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Faculty Research Profiles

The research theme that links the members of the CRBM together is the regenerative biology and medicine of complex structures, such as the central nervous system, musculoskeletal system, liver and pancreas of mammals, and the central nervous system and appendages of amphibians, which are uniquely able to regenerate these structures naturally.

Learn more about faculty research programs, scientific and commercial advisory board members, graduate study, and tech transfer by clicking on the links below:

Teri Belecky-Adams

Teri Belecky-Adams
  • Assistant Professor

Department of Biology
School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan St.
Indianapolis, IN 46202

Phone: (317) 278-5715
Fax: (317) 274-2846
Email: tbadams@iupui.edu

Research Interests

Development of a functional eye involves two basic processes. First, a homogeneous undifferentiated population of cells must be induced to acquire specific cell fates. Second, cells must also have a sense of where they lie within the retina (a process known as patterning) in order to form proper topographical connections with the rest of the brain. A loss of either one of these processes can lead to a loss of vision. My lab is focused on understanding the roles of a large family of proteins, known as the TGF-Beta family of growth factors, in the differentiation and patterning of the vertebrate eye. We are using tools such as microinjection of retroviruses carrying transgenes into the developing eye, as well as addition of factors in vitro to retinal cultures to perturb growth factor signaling to assay effects on differentiation as well as axonal and dendritic outgrowth. By understanding the mechanisms whereby cells differentiate and form connections, we will one day be able to understand and apply this knowledge to eradicate congenital defects and treat injured or degenerating neurons.

Recent Publications

  • Sehgal, R, Andres, D, Adler, R, and Belecky-Adams, TL (2006) Bone Morphogenetic Protein 7 Increases Chick Photoreceptor Outer Segment Initiation. Invest Ophthalmol Vis Sci. 47:3625-34.
  • Fong, SL, Criswell, MH, Belecky-Adams, T, Fong, WB, McClintick, JN, Kap, WW, and Edenberg, HJ (2005) Characterization of a transgenic mouse line lacking photoreceptor development within the ventral retina. Exp Eye Res. 2005 Oct;81(4):376-88.
  • Belecky-Adams, T.L. Michael Holmes, Yuqing Shan, C. Susan Tedesco, Carla Mascari, Ajay Kaul, David C. Wight, Randal E. Morris, Mark Sussman, Jack Diamond, Linda M. Parysek (2003) An Intact Intermediate Filament Network is Required for Collateral Sprouting of Small Diameter Nerve Fibers. J. Neurosci. 23, 9312-9319.
  • Adler, R. and Belecky-Adams, T. L. (2002). The role of bone morphogenetic proteins in the differentiation of the ventral optic cup. Development 129, 3161-71.
  • Belecky-Adams, T., Adler, R. and Beebe, D. (2002). Bone morphogenetic protein signaling and the initiation of lens fiber cell differentiation. Development 129, 3795-802.

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Jo Ann Cameron, PhD, Affiliate Faculty

Jo Ann Cameron
  • Associate Professor, Department of Cell and Developmental Biology and College of Medicine
  • Core Faculty Member, Regenerative Biology and Tissue Engineering
  • Regeneration Research Theme, Institute for Genomic Biology, University of Illinois at Urbana-Champaign

Institute for Genomic Biology
Room 2103
1206 West Gregory Drive, Urbana, IL 61801

Phone: (217) 333-1254
Fax: (217) 244-1800
Email: joanncam@uiuc.edu

Research Interests

We are conducting studies that will provide insight into why most adult vertebrates, including humans, lose the ability to regenerate their limbs. The same principles that apply to developing systems often hold true for regenerating systems. Our laboratory has a long-standing interest in how vertebrate limb pattern is established during development and regeneration. Successful vertebrate limb regeneration is accomplished by formation, continued growth, patterning, and differentiation of a regeneration blastema at the cut surface of a limb stump. Mature tissues adjacent to the amputation surface lose their extracellular matrix and cells re-enter the cell cycle in preparation for stump repair and regeneration of lost parts. At the cellular level a regeneration blastema resembles the original embryonic limb bud that gives rise to the mature limb. Presently, we are examining initial cellular and molecular events in the stump following partial hindlimb amputation in pre-metamorphic and metamorphic Xenopus laevis (African Clawed Frog). Pre-metamorphic tadpoles can regenerate hindlimb parts, while the ability to regenerate declines as the tadpole undergoes metamorphosis. Tadpole hindlimb regeneration provides a natural loss-of-function system that resembles the typical loss of ability to regenerate in vertebrates. We are studying cellular and molecular features of blastemas at the developmental stages and amputation levels where there is predictably “good regeneration” and where there is predictably “poor” regeneration. Blastemas with characteristics most closely resembling limb buds are more likely to regenerate successfully. One hypothesis we are investigating is that the cellular and molecular features of “good” and “poor” blastemas can be used to predict whether a particular blastema will regenerate more or less completely. From our work and the work of other investigators we know that many of the same genes important during embryonic limb development are expressed again during limb regeneration. Patterning factors like sonic hedgehog, Hox genes and Msx, and growth factors like Fgfs are expressed during limb regeneration. Expression of these genes provides cell-signaling centers within limb buds at each developmental stage and similar centers within regeneration blastemas during regeneration. Particular genes may not be expressed or their expression pattern may change when regeneration fail.

Recent Publications

  • Wolfe, A, Nye, HDL and Cameron, JA. 2000. Extent of ossification at the amputation plane is correlated with the decline of blastema formation and regeneration in Xenopus Laevis hindlimbs. Dev. Dynamics, 218:681-697.
  • Chernoff EAG, Stocum DL, Nye HLD, Cameron JA. 2003. Urodele spinal cord regeneration and related processes. Dev. Dynamics 226:295-307.
  • Nye HLD, Cameron JA, Chernoff EAG, Stocum DL. 2003. Regeneration of the urodele limb: a review. Dev. Dynamics 226:280-294.
  • Wolfe AD, Crimmins G, Cameron, JA, Henry JJ. 2004. Early Regeneration Genes: Building a Molecular Profile for Shared Expression in Cornea-Lens Transdifferentiation and Hind Limb Regeneration in Xenopus laevis. Dev. Dynamics, 230: 615-629.
  • Nye, HLD, Cameron JA. 2005. Strategies to Reduce Variation in Xenopus laevis Regeneration Studies. Dev. Dynamics. 234:151-158

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Ellen A.G. Chernoff, PhD

Ellen A.G. Chernoff
  • Associate Professor of Biology
  • Adjunct faculty, Stark Institute for Neuroscience

Dept. of Biology, School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan St.
Indianapolis, IN 46202-5132

Phone: (317) 274-0591
Fax: (317) 274-2846
Email: echernof@iupui.edu

Research Interests

My laboratory studies amphibian spinal cord and limb regeneration. We examine spinal cord and limb regeneration using the frog Xenopus laevis, and a salamander, the axolotl (Ambystoma mexicanum). Projects include characterizing the stem cell properties of spinal cord and expression of dorsoventral patterning genes in regeneration. We also study the involvement of stem cells in amphibian limb regeneration as an alternative to the involvement of dedifferentiation in this process. We are comparing differences at different stages of the life cycle. Frog tadpoles lose their ability to regenerate as they approach metamorphosis, and we compare regenerating and non-regenerating tissue. Salamanders regenerate even as adults, so we can compare regeneration in larval, juvenile and adult animals. Lastly, we are comparing the role of stem cells in regeneration between normal axolotls and the mutant short-toes (s/s) which can regenerate spinal cord and tail, but not limbs.

Recent Publications

  • Chernoff EAG, Sato K, Corn A and Karcavich RE (2002) Spinal Cord Regeneration: Intrinsic Properties and Emerging Mechanisms. Sem Cell Develop Biol 13:361-368
  • Nye HL, Cameron J, Chernoff EAG and Stocum DL. (2003) Regeneration of the Urodele Limb: A Review. Develop. Dyn. 226:280-294.
  • Nye HLD, Cameron, J., Chernoff EAG and Stocum DL (2003) Extending theTable of Stages of Normal Development of the Axolotl: Limb Development. Devel Dyn 226:555-560 (Cover picture).
  • Showalter AD, Yaden BC, Chernoff EAG and Rhodes SJ (2003) Cloning and Analysis of Axolotl ISL2 and LHX2 LIM-Homeodomain Transcription Factors. Genesis (Developmental Genetics) 38:110-121.
  • Johnson CD, Narasimha Chary S, Chernoff EA, Zeng Q, Running MP, Crowell DN. (2005) Protein Geranylgeranyltransferase I Is Involved in Specific Aspects of Abscisic Acid and Auxin Signaling in Arabidopsis. Plant Physiol. 139:722-733.

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Guoli Dai, DVM, PhD

Guoli Dai
  • Assistant Professor of Biology

Department of Biology, School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan Street
Indianapolis, IN 46204

Phone: (317) 278-3895
Fax: (317) 274-2846
Email: gdai@iupui.edu

Research Interests

My laboratory investigates the molecular mechanisms regulating hepatocyte proliferation and liver growth in both physiological and pathological conditions. The maternal liver adapts to pregnancy by marked growth manifested by hepatocyte proliferation and liver size increase. We are particularly interested in revealing the role of placental hormones in mediating the hepatic growth response to pregnancy. In response to acute or chronic liver injuries, the liver regenerates, repairing damaged tissue and restoring original structures and functions. The hepatic regenerative response is a phenomenon of compensatory growth of injured liver. Timely and/or enhanced hepatocyte proliferation leads to recovery from liver injury and survival, whereas delayed and/or inhibited hepatocyte proliferation in pathological conditions results in liver failure and death. We are studying the functions of transcription factors that can be activated by a pharmacological approach in modulating hepatocyte proliferation during liver regeneration. Our goal is to develop a clinical strategy to rescue injured livers by targeting hepatocyte proliferation and thereby liver repair.

Recent Publications

  • G Dai, L Lu, S Tang, N Sahgal, and M Soares. 2002. Prolactin Family Miniarray: A Tool for Evaluating Uteroplacental-trophoblast Endocrine Cell Phenotypes. Reproduction, 24(6):755-65.
  • R Ain, G Dai, J Dunmore, A Godwin, and M Soares. 2004. A Prolactin Pamily Paralog Regulates Reproductive Adaptations to A Physiological Stressor. Proc. Natl. Acad. Sci. U S A., 23;101(47):16543-8.
  • G Dai and YJ Wan. 2005. Animal Models of Xenobiotic Receptors. Current Drug Metabolism, 6(4):341-355.
  • G Dai, N Chou, L He, MA Gyamfi, JA Mendy, AL Slitt, CD Klaassen, and YJ Wan. 2005. Retinoid X Receptor Alpha Regulates the Expression of Glutathione S-transferase Genes and Modulates Acetaminophen-glutathione Conjugation in Mouse Liver. Molecular Pharmacology, 68(6):1590-1596.
  • G Dai, N Chou, L He, and YJ Wan. 2006. Acetaminophen Metabolism Does Not Contribute to Gender Difference in Its Hepatotoxicity in Mouse. Toxicological Sciences, 92(1):33-41.
  • SM Alam, T Konno, G Dai, L LU, D Wang, JH Dunmore, AR Godwin, MJ Soares. 2007. A Uterine Decidual Cell Cytokine Ensures Pregnancy-dependent Adaptations to A Physiological Stressor. Development, 134(2):407-15.
  • J Bustamante, G Dai, and MJ Soares. 2008. Pregnancy and Lactation Modulate Maternal Splenic Growth and Development of the Erythroid Lineage in the Rat and Mouse. Reproduction, Fertility and Development, 20(2):303-310.
  • G Dai, L He, P Bu, and YJ Wan. 2008. Pregnane X Receptor Is Required for Normal Progression of Liver Regeneration. Hepatology, 47(4):1276-1287

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Brittney-Shea Herbert, Ph.D.

Brittney-Shea Herbert
  • Assistant Professor of Medical and Molecular Genetics
  • Member of the Indiana University Melvin and Bren Simon Cancer Center

Dept of Medical and Molecular Genetics
Indiana University Melvin and Bren Simon Cancer Center
Indiana University School of Medicine
975 W. Walnut St., IB 242
Indianapolis, IN 46202

Phone: (317) 278-6147
Fax: (317) 274-1069
Email: brherber@iupui.edu

Research Interests

The major research interest of my laboratory is in the role of telomerase in aging and cancer. Telomerase is a ribonucleoprotein complex that aids in the maintenance of telomeres. Telomeres provide a protective cap for the ends of chromosomes to prevent fusions and recognition as damaged DNA. Most somatic cells do not contain telomerase activity. However, telomerase activity is present in cells with the indefinite potential to replicate, such as stem, germ, and cancer cells. As telomerase can play a role in the replicative potential of stem cells, which is currently undergoing intensive research, it is important to understand how telomerase is regulated. Furthermore, telomerase expression may be used in the study of tissue regeneration. Induced expression of telomerase results in the immortalization of normal cells and these cells can be expanded and induced to differentiate. Conversely, inhibition of telomerase in cancer cells results in the reduction of cell growth, tumor formation, and metastases in vitro and in vivo. Therefore, telomerase represents not only a tool for regenerative biology, but also a target for cancer therapy. We are currently investigating the role of telomerase in cell growth and the replicative potential in normal and cancerous cells using natural/ synthetic compounds or DNA/RNA molecules (such as thio-phosphoramidates and microRNAs) that can regulate telomerase activity.

Recent Publications

  • Herbert B-S, Hochreiter AE, Wright WE, Shay JW (2006) Non-radioactive detection of telomerase activity using the Telomeric Repeat Amplification Protocol (TRAP). Nature Protocols 1: 1583-1590.
  • Lewis C*, Herbert B-S* (*co-first authors), Bu D, Halloway S, Beck A, Shadeo A, Ashfaq R, Brekken R, Lam W, Shay JW, Euhus D (2006) Telomerase immortalization of human mammary epithelial cells derived from a BRCA2 mutation carrier. Breast Cancer Research and Treatment 99:103-115.
  • Herbert B-S, Gellert G, Hochreiter A, Pongracz K, Wright WE, Zielinska D, Chin A, Harley CB, Shay JW, Gryaznov SM (2005) Lipid modification of GRN163, an N3’?P5’- thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition. Oncogene 24:5262-5268.
  • Hochreiter AE, Xiao H, Goldblatt EM, Gryaznov SM, Miller KD, Badve S, Sledge GW, Herbert B-S (2006) The telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth and metastasis of breast cancer. Clinical Cancer Research 12: 3184-3192.
  • Gomez-Millan J, Goldblatt EM, Gryaznov S, Mendonca MS, Herbert B-S (2007). Specific telomere dysfunction induced by GRN163L increases radiation sensitivity in breast cancer cells. International Journal of Radiation Oncology, Biology, Physics 67: 897-905.

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Michael W. King, PhD

Michael W. King
  • Professor

Indiana University School of Medicine Terre Haute
Center for Regenerative Biology and Medicine
Room 135HH
Terre Haute, IN. 47809

Phone: (812) 237-3417
Fax: (812) 237-7646
E-mail: miking@iupui.edu

Research Interests

Research being conducted in Dr. King's laboratory involves the isolation and characterization of novel proteins whose functions may regulate tissue regeneration. We are using the frog Xenopus laevis as a model. In this species limbs regenerate well during larval stages, but gradually lose this ability as the animal approaches metamorphosis. Adult frogs do not regenerate and the response of these structures to surgical transection is normally similar to that of higher vertebrates (i.e. scarring). This stage difference in regenerative ability can be used to advantage experimentally to discover, by differential gene screening, the molecules and molecular pathways that drive regeneration or inhibit regeneration within the same species. Long-term goals of this research are to identify mechanisms by which control over regeneration regulating genes can be exerted. The aim is that by manipulating these genes in humans we will be able to stimulate tissue repair and regeneration.

Recent Publications

  • Alshaibi, N, King, MW, Duong, T, and Ghosh, SK 2007 DP58, an inducible myeloid protein, is constitutively expressed in murine neuronal nuclei. Frontiers of Bioscience 12:2947-295
  • Grow, MW, Neff, AW, Mescher, AL and King, MW 2006 Global analysis of gene expression in Xenopus hindlimbs during stage-dependent complete and incomplete regeneration. Dev. Dyn. 235:2667-2685
  • Neff, AW, King, MW, Harty, MW, Nguyen, T, Calley, J, Smith, RC and Mescher, AL, 2005 Expression of Xenopus XlSALL4 during limb development and regeneration. Dev. Dyn. 233:356-367
  • Harty, M, Neff, AW, King, MW, and Mescher, AL 2003 Regeneration or Scarring: An Immunological Perspective. Dev. Dyn. 226: 268-279
  • King, MW, Nguyen, T, Calley, J, Harty, MW, Muzinich, MC, Mescher, AL, Chalfant, C, N'Cho, M, McLeaster, K, McEntire, J, Stocum, D, Smith, RC, Neff, AW 2003 Identification of genes expressed during Xenopus laevis limb regeneration using subtractive hybridization. Dev. Dyn. 226: 398-409

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Jiliang Li, MD, PhD

Jiliang Li
  • Assistant Professor

Department of Biology
School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan St.
Indianapolis, IN 46202-5132

Phone: (317) 278-1163
Fax: (317) 274-2846
E-mail: jilili@iupui.edu

Research Interests

My research interests are in bone cell biology and bone regeneration. For several years I have studied the mechanisms by which exercise builds bone with the goal of identifying novel drug targets linked to increased bone strength. My research activities include the study of the biological and mechanical aspects of bone using animal models and cell cultures, as well as the study of molecular and cellular mechanisms of mechanotransduction, the process of conversion of mechanical signals into biological signals in bone cells. I am also involved in studying pharmaceutical treatments for osteoporosis and bone fracture. In addition, I am planning to study biology of bone marrow mesenchymal stem cell and its role in bone regeneration.

Recent Publications

  • Sawakami K, Robling AG, Ai M, Pitner ND, Liu D, Warden SJ, Li J, Maye P, Rowe DW, Duncan RL, Warman ML, Turner CH 2006 The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J Biol Chem. 18;281(33):23698-711.
  • Castillo AB, Alam I, Tanaka SM, Levenda J, Li J, Warden SJ, Turner CH. 2006 Low-amplitude, broad-frequency vibration effects on cortical bone formation in mice. Bone. 39(5):1087-96.
  • Iwata K, Li J, Follet H, Burr DB 2006 Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia, Bone, 39(5):1053-8.
  • Li J, Liu D, Ke HZ, Duncan RL, Turner CH 2005 Osteogenesis after mechanical loading is linked to the P2X7 nucleotide receptor. J Biol Chem, 280(52):42952-9.
  • Li J, Miller MA, Hutchins GD, Burr DB 2005 Imaging bone microdamage in vivo with positron emission tomography. Bone 37(6):819-24.

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Bingbing Li, PhD, Affiliate Faculty

Bingbing Li
  • Assistant Professor

Department of Chemistry
Central Michigan University
201 E. Ottawa Ct.
Mt. Pleasant, MI 48859

Phone: (989) 774-3441
Fax: (989) 774-3883
E-mail: li3b@cmich.edu

Research Interests

The development of smart biomaterials requires a precise knowledge of interfacial interactions of polymer implants with the surrounding biological environment. The goal of our lab is to design, fabricate, and evaluate intelligent textiles and functional nanocomposites for orthopedic and dental applications in regenerative medicine, with an emphasis on understanding bio-interfacial phenomena such as wetting, adhesion, diffusion, crystallization, and degradation.

Recent Publications

  • N. Rao, D. Jhamb, D. Milner, B. Li, F. Song, M. Wang, R. Voss, M. King, M. Palakal, B. Saranjami, H. Nye, J. A. Cameron, and D. Stocum, “Proteomic Analysis of Blastema Formation in Regenerating Axolotl Limbs”, 2009, Submitted to BMC Biology.
  • B. Li, H. Marand, A. R. Esker, “Dendritic growth of poly(Ɛ-caprolactone) crystals from compatible blends with poly(t-butyl acrylate) at the air/water interface”, Journal of Polymer Sciences B: Polymer Physics 2007, 45, 3200.
  • B. Li, A. R. Esker, “Molar mass dependent growth of poly(Ɛ-caprolactone) crystals in Langmuir films”, Langmuir 2007, 23, 2546.
  • B. Li, A. R. Esker, “Blends of poly(Ɛ-caprolactone) and intermediate molar mass polystyrene as Langmuir films at the air/water interface”, Langmuir 2007, 23, 574.
  • B. Li, Y. Wu, M. Liu and A. R. Esker, “Brewster angle microscopy study of poly(Ɛ-caprolactone) crystal growth in Langmuir films at the air/water interface”, Langmuir 2006, 22, 4902.
  • S. Ni, W. Lee, B. Li, A. R. Esker, “Thermodynamics of the liquid expanded to condensed phase transition of poly(L-lactic acid) in Langmuir monolayers”, Langmuir 2006, 22, 3672.
  • Y. Wu, B. Li, W. Wang, F. Bai, M. Liu, “Coordination assisted molecular assemblies of perylene- 3,4,9,10-tetracarboxylic acid with Copper (II) ion at the air/water interface”, Materials Sciences and Engineering: C: Biomimetic and Supramolecular Systems 2003, 23, 605

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James A. Marrs, PhD

James A. Marrs
  • Associate Professor

Department of Biology
School of Science
723 W. Michigan St.
Indianapolis, IN 46202

Phone: (317) 278-0031
Fax: (317) 274-2846
E-mail: jmarrs@iupui.edu

Research Interests

My research laboratory studies the roles of cell-cell junctional complexes (adherens junctions and tight junctions) in the establishment and maintenance of epithelial cell polarity and the role of cadherin cell adhesion molecules during embryogenesis. Cadherins are a large superfamily of molecules which mediate calcium dependent cell-to-cell adhesion, and these molecules regulate cell adhesiveness, cell survival, cell polarity and cellular differentiation during normal development and during disease processes.

We are also investigating defects in developmental mechanisms produced by ethanol exposure during embryogenesis. Our experiments and those from other laboratories show that zebrafish can be used to model fetal alcohol syndrome (FAS). As ongoing and new animal model research promotes better understanding of the consequences of fetal ethanol exposure in human patients, a key goal is to gain new mechanistic insight into the genesis of FASD. Information gained from novel approaches in animal models will facilitate translational research, with a long-term goal of developing rational approaches to treatment and prevention of this devastating disorder.

Recent Publications

  • Liu Q, Londraville RL, Azodi E, Babb SG, Chiappini-Williamson C, Marrs JA, Raymond PA (2002) Up-regulation of cadherin-2 and cadherin-4 in regenerating visual structures of adult zebrafish. Exp Neurol 177: 396-406.
  • Babb, SG and Marrs JA (2004) E-cadherin regulates cell movements and tissue formation in early zebrafish embryos. Developmental Dynamics 230: 263-277.
  • Babb SG, Kotradi SM, Shah B, Chiappini-Williamson C, Bell LN, Schmeiser G, Chen E, Liu Q and Marrs JA (2005) Zebrafish R-cadherin (Cdh4) controls visual system development and differentiation. Developmental Dynamics 233: 930-945.
  • Gopalakrishnan S, Hallett MA, Atkinson S, Marrs JA (2006) aPKC-Par complex dysfunction and tight junction disassembly in renal epithelial cells during ATP-depletion. Am J Physiol Cell Physiol 292: C1094-102.
  • Babb-Clendenon S. G., Y.-c. Shen, Q. Liu, K. E. Turner, M. S. Mills, G. W. Cook, C. A. Miller, V. H. Gattone II, K. F. Barald, and J. A. Marrs. 2006. Cadherin-2 participates in the morphogenenesis of the zebrafish inner ear. J. Cell Sci. 119: 5169-5177.
  • Liu Q, Frey RA, Babb-Clendenon SG, Liu B, Francl J, Wilson AL, Marrs JA, and Stenkamp DL (2007) Differential expression of photoreceptor-specific genes in the retina of a zebrafish cadherin2 mutant glass onion and zebrafish cadherin4 morphants. Exp Eye Res. 84: 163-175.
  • Wilson AL, Shen Y, Babb-Clendenon SG, Rostedt J, Liu B, Barald KF, Marrs JA, and Liu Q (2007) Cadherin4 plays a role in the development of zebrafish cranial ganglia and lateral line system. Developmental Dynamics 236: 893-902.

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Anthony L. Mescher, PhD

Anthony L. Mescher
  • Professor

Medical Sciences Program
Jordan Hall 202
Indiana University Bloomington
Bloomington, IN 47405

Phone: (812) 855-4693
Fax: (812) 855-4436
Email: mescher@indiana.edu

Research Interests

Current research in the Mescher lab involves the interface between the inflammatory effects of amputation injury and the molecular events leading to epimorphic regeneration of amphibian limbs. Specifically, we are studying (1) the nature of genes expressed in the early post-amputation period in regenerating hindlimbs of larval frogs, with particular interest in genes related to inflammation, immunity, and dedifferentiation, (2) differences in expression of such genes between young larvae which regenerate limbs completely and older larvae with defective regeneration, in an attempt to elucidate the ontogenic loss of regenerative capacity, and (3) expression patterns and control of genes with an apparent role in both dedifferentiation and limb patterning. Dr. Mescher also maintains strong interest in the molecular basis of both the apical epithelial effect and the nerves’ trophic effect on blastema cell proliferation, which are required for epimorphic regeneration but remain incompletely understood.

Recent Publications

  • AL. Mescher, W L. Wolf, E., A. Moseman, B. Hartman, C. Harrison, E. Nguyen, and AW. Neff (2007) Cells of cutaneous immunity in Xenopus: Studies during larval development. Dev Comp Immunol (in press)
  • Grow MW, Neff AW, Mescher AL, King MW. (2006) Global analysis of gene expression in Xenopus limbs during stage-dependent complete and incomplete regeneration. Dev Dyn 235:2667-2685.
  • Mescher AL, Neff AW (2005). Regenerative capacity and the developing immune system. Adv Bioch Eng/ Biotech 93:39-66.
  • Neff AW, King MW, Harty MW, Nguyen T, Calley J, Smith RC, Mescher AL. (2005) Expression of Xenopus XlSALL4 during limb development and regeneration. Dev Dyn 233(2):356-367.
  • Harty, M, AW Neff, MW King, and AL Mescher (2003) Regeneration or scarring: An immunologic perspective. Dev Dyn 226:268-279

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Raghu G. Mirmira, MD, PhD

Raghu G. Mirmira
  • Associate Professor

Department of Pediatrics
Department of Medicine
Department of Cellular and Integrative Physiology
Office address: MS2031
Lab address: MS2021

Phone: (317) 274-4145
Fax: (812) 855-4436
Email: rmirmira@iupui.edu
Web: http://www.iupui.edu/~islets

Research Interests

It is widely known now that the prevalence of diabetes has been rising to alarming rates in the United States. The American Diabetes Association reports that almost 21 million Americans (7% of the US population) have diabetes. The pathophysiology of diabetes is complex, but it is clear that defects at the level of the insulin-producing islets underlie the development of the disorder in nearly all forms of diabetes. Thus, my laboratory focuses on the regulation of gene transcription during pancreatic islet development, function, and survival. The goal of this research is to allow for the endogenous regeneration of pancreatic islets in individuals with diabetes. The projects in my laboratory fall into three main categories:

  • the role of homeodomain transcription factors, basic helix-loop-helix transcription factors, and PPAR-gamma during the development of islets and the pathogenesis of islet dysfunction in type 1 and type 2 diabetes, and in islet regeneration,
  • the interrelationships between chromatin structure and gene transcription in the mature
  • the role of post-transcriptional mechanisms in cytokine-mediated islet dysfunction.

We believe that intervening at any of these three stages in the islet life-cycle (development, function, and survival) will allow for the regeneration of islets for the treatment of diabetes. Toward this effort, my lab has also engaged in translational work that would bring new therapies developed by us or our collaborators into the clinic to treat patients with diabetes. These areas of research include bench and bedside testing of new inhibitors of the islet inflammatory intermediates (including 12-lipoxygenase, lisofylline, and eukaryotic translation initiation factor 5A)

Recent Publications

  • Iype, T, Francis, J, Garmey, JC, Schisler, J, Nesher, R, Weir, GC, Becker, TC, Newgard, CB, Griffen, SC, and Mirmira, RG. Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1. Application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. J. Biol. Chem. 280:16798 (2005)
  • Taylor, D.G., Babu, D., and Mirmira, R.G. The C-Terminal Domain of the b Cell Homeodomain Factor Nkx6.1 Enhances Sequence-Selective DNA Binding at the insulin Promoter. Biochemistry 44:11269 (2005)
  • Francis, J., Chakrabarti, S.K., Garmey, J.C., and Mirmira, R.G. Pdx-1 links histone H3-K4 methylation to RNA polymerase II elongation during activation of insulin gene transcription J. Biol. Chem. 280:36244 (2005)
  • Francis, J., Babu, D., Deering, T., Chakrabarti, S., Taylor, D., Garmey, J., Evans-Molina, C., and Mirmira, R.G. Role of chromatin accessibility in the occupancy and transcription of the insulin gene by the pancreatic transcription factor Pdx-1. Mol. Endocrinol. 20:3133 (2006)
  • Evans-Molina, C, Garmey, JC, Ketchum, R, Brayman, KL, Deng, S, and Mirmira, RG. Glucose Regulation of Human Insulin Gene Transcription and Pre-mRNA Processing. Diabetes 56:827 (2007)
  • Babu, D.A., Deering, T.G., and Mirmira, R.G. A feat of metabolic proportions: Pdx1 orchestrates cellular development, growth, and function in the mammalian pancreas. Mol. Genet. Metab. 92:43 (2007)
  • Babu, D.A., Chakrabarti, S.K., Garmey, J.C., and Mirmira, R.G. Pdx1 and BETA/NeuroD1 participate in a transcriptional complex that mediates short-range DNA looping at the insulin gene. J. Biol. Chem. 283 :8164 (2008).
  • Antkowiak, P.F., Tersey, S.A., Carter, J.D., Vandsburger, M.H., Nadler, J.L., Epstein, F.H., and Mirmira, R.G. Non-invasive Assessment of Pancreatic ß Cell Function In Vivo Using Manganese-Enhanced Magnetic Resonance Imaging. Am. J. Physiol. Endo. Met., 2009 (In Press).
  • Evans-Molina, C., Robbins, R., Kono, T., Tersey, S., Vestermark, G., Nunemaker, C., Garmey, J.C., Deering, T.G., Keller, S.R., Maier, B., and Mirmira, R.G. PPAR-gamma activation restores islet function in diabetic mice through reduction of ER stress and maintenance of euchromatin structure. Mol. Cell. Biol., 2009 (In Press).
  • Evans-Molina, C., Vestermark, G., and Mirmira, R.G. Development of Insulin Producing Cells From Primitive Biologic Precursors. Curr. Op. Organ Transpl. 2009 (In Press)

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Anton W. Neff, PhD

Anton W. Neff
  • Professor

Medical Sciences Program
Jordan Hall 202
Indiana University Bloomington
Bloomington, IN 47405

Phone: (812) 855-7055
Fax: (812) 855-4436
Email: neff@indiana.edu

Research Interests

The Neff lab is interested in the molecular and cellular interactions required for tissue and organ regeneration utilizing amphibian model systems. Current work involves differential genomics and proteomics to identify limb regeneration regulatory pathways with emphasis on immunomodulatory and stem cell establishment/maintenance pathways.

Recent Publications

  • Harty, M., A.W. Neff, M.W. King, and A.L. Mescher (2003) Regeneration or scarring: An immunologic perspective. Dev. Dyn 226:268-279
  • King, M.W., T. Nguyen, J. Calley, M.W. Harty, M.C. Muzinich, A.L. Mescher, C. Chalfant, M. N’Cho, K. McLeaster, J. McEntire, D. Stocum, R.C. Smith, and A.W. Neff. (2003) Identification of genes expressed during Xenopus laevis limb regeneration by using subtractive hybridization. Dev. Dyn 226:398-409
  • Mescher AL, Neff AW (2005). Regenerative capacity and the developing immune system. Adv. Biochemical Engineering/ Biotechnology 93:39-66.
  • Neff AW, King MW, Harty MW, Nguyen T, Calley J, Smith RC, Mescher AL. (2005) Expression of Xenopus XlSALL4 during limb development and regeneration. Dev Dyn. 233(2):356-367.
  • Grow MW, Neff AW, Mescher AL, King MW. (2006) Global analysis of gene expression in Xenopus limbs during stage-dependent complete and incomplete regeneration. Dev. Dyn. 235:2667-2685.
  • AL. Mescher, W L. Wolf, E., A. Moseman, B. Hartman, C. Harrison, E. Nguyen, and AW. Neff (2006) Cells of cutaneous immunity in Xenopus: Studies during larval development. Developmental and Comparative Immunology (Epub ahead of print).

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Mathew Palakal, PhD

Mathew Palakal
  • Associate Dean, Research & Graduate Programs, School of Informatics
  • Director, Informatics Research Institute
  • Professor of Computer Science

School of Informatics
Indiana University-Purdue University Indianapolis
535 W. Michigan St. IT 475
Indianapolis, IN 46202

Phone: (317) 278-7689
Fax: (317) 278-4140
Email: mpalakal@cs.iupui.edu

Research Interests

The biomedical literature databases continue to grow rapidly with vital information that is important for conducting sound biomedical research. BioMap is an attempt to create a scalable knowledgebase of biological relationships from vast amount of literature data. The development of BioMap system addresses several innovative research issues related to knowledge discovery from literature documents and real-time, interactive access of this knowledge. Specific problems that are being investigated are: identification of multiple biological objects and discovering their direct, transitive and directional relationships and generating pathways of new hypothesis using the hypergraph based on graph algorithms. Protein-protein, gene-protein, disease-drug interactions are examples of biological associations that are automatically discovered from large number of literature documents. These associations are further validated using computational techniques. BioMap can discover interactions in specific biomedical problem domains such as inflammatory diseases, regenerative biology, and cancer.

Recent Publications

  • Naidu, P., Palakal, M., and Hartanto, S: On-the-fly data integration models for biological databases, 2007 ACM Symposium on Applied Computing, Korea, in press, 2007.
  • Palakal M, Bright J, Sebastian T, Hartanto S: A Comparative Study of Cells in Inflammation, EAE and MS using BioMedical Literature Data Mining. Journal of Biomedical science (in press), 2006.
  • Palakal M, Mukhopadhyay S,Stephens M: Identification of Biological Relationships from Text Documents. Book Chapter in "Medical Informatics: Advances in Knowledge Management and Data Mining in Biomedicine, Ed. H. Chen. Kluwer Publishers, 449, 2005.
  • Jayadevaprakash, N., Mukhopadhyay, S., and Palakal, M: An Approach to Generating Association Graphs of Non-Co-Occurring Text Objects using Transitive Methods, 20th ACM Symposium on Applied Computing, 2005.
  • Kumar, K., Palakal, M., Mukhopadhyay, S., BioMap: Toward the Development of a Knowledge Base of Biomedical Literature, 2004 ACM Symposium on Applied Computing, Nicosia, Cyprus, 2004.
  • Palakal M, Stephens M, Mukhpodhyay S, Raje R, Rhodes S: Identification of Biological Relationships from text documents using efficient computational Methods. Journal of Bioinformatics and Computational Biology, 2003,1, (2) , 1.

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Simon J. Rhodes, PhD

Simon J. Rhodes
  • Professor, Department of Cellular and Integrative Physiology
  • Professor, Department of Biochemistry and Molecular Biology
  • Associate Dean for Graduate Studies, Indiana University School of Medicine
  • Adjunct Professor, Department of Biology

Medical Science Building Room 207
Indiana University School of Medicine
Indiana University-Purdue University Indianapolis
635 N. Barnhill Drive
Indianapolis, IN 46202-5120

Phone: (317) 274-3441
Fax: (317) 278-5211
Email: srhodes@iupui.edu

Research Interests

Our laboratory investigates how key regulatory genes direct the determination and differentiation of individual endocrine cell lineages of the brain and pituitary during vertebrate development. For example, the anterior pituitary gland presents a valuable model system to pursue these studies. The mature gland contains five discrete cell types that are each characterized by the secretion of specific polypeptide hormones critical for growth, sexual function, lactation, thyroid activity, adrenal physiology and homeostasis. We use both molecular/ in vitro and transgenic animal approaches to examine the roles of several classes of transcription factors in specification of pituitary cell phenotypes. Our research goals include:

1. Characterization of the basic biology/biochemistry of endocrine transcription factors.
2. Investigation of the molecular nature of human pituitary diseases, such as pituitary tumors and growth disorders in children, in collaboration with faculty at Riley Children's Hospital.
3. The analysis of the gene regulatory pathways that control growth, metabolism, and reproductive fitness in agricultural species, in collaboration with the U.S. Meat Animal Research Center.

Other projects in the lab include investigation of bone transcription factors in collaboration with Dr. Joseph Bidwell of the Indiana University School of Medicine at IUPUI, and molecular studies of nervous system regeneration in amphibians in collaboration with Dr. Ellen Chernoff of the IUPUI Biology Department.

Recent Publications

  • Savage, J.J., Mullen, R.D., Sloop, Colvin, S.C., Camper, S.A., Franklin, C.L. and Rhodes, S.J. (2007). Transgenic Mice Expressing LHX3 Transcription Factor Isoforms in the Pituitary: Effects on the Gonadotrope Axis and Sex-Specific Reproductive Disease. J. Cell. Physiol, In Press.
  • Mullen, R.D., Colvin, S.C., Hunter, C.H., Savage, J.J., Walvoord, E.C., Bhangoo, A.P.S., Ten, T., Weigel, J., Pfäffle, R.W., and Rhodes, S.J. (2007). Roles of the LHX3 and LHX4 LIM-homeodomain factors in pituitary development. Mol. Cell. Endocrinol. in press.
  • Durán-Prado, M., Bucharles, C., Gonzalez, B.J., Vázquez-Martínez, R., Martínez-Fuentes, A.J., García-Navarro, S., Rhodes, S.J. Vaudry, H., Malagón, M.M., and Castaño, J.P. 2006. Porcine somatostatin receptor 2 displays typical pharmacological sst2 features but unique dynamics of homodimerization and internalization. Endocrinology, in press.
  • Granger, A., Bleux, C., Kottler, M.-L., Rhodes, S.J., Counis, R., and Laverrière, J.-N. (2006). The LIM-homeodomain proteins Isl-1 and Lhx3 act with steroidogenic factor-1 to enhance gonadotrope-specific activity of the gonadotropin-releasing hormone receptor gene promoter. Mol. Endocrinol. 20: 2093-2108. Epub 2006 Apr 13.
  • Bhangoo, A.P.S., Hunter, C.S., Savage, J.J., Anhalt H, Pavlakis S, Walvoord E.C., Ten, S., and Rhodes, S.J. (2006). A novel LHX3 mutation presenting as combined pituitary hormonal deficiency. J. Clin. Endocrinol. Metab. 91: 747-753. Epub 2006 Jan 4.

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Randall J. Roper, PhD

Randall J. Roper
  • Assistant Professor

Department of Biology
School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan St., SL306
Indianapolis, IN 46202

Phone: (317) 274-8131
Fax: (317) 274-2846
E-mail: rjroper@iupui.edu

Research Interests

The neural crest is a transient population of cells found during early embryogenesis and has been termed the “fourth germ layer” because of its developmental mulitpotency. Several tissues with a neural crest component, including craniofacial skeleton, peripheral nervous system, heart, and digestive tract, are affected in individuals with Down syndrome. It has therefore been hypothesized that trisomy 21 causes defects in neural crest cells (NCC). Our work with mouse models of Down syndrome provided the first experimental evidence that trisomy affects neural crest precursors of craniofacial skeleton. Our laboratory is interested in understanding how dosage imbalance of genes on human chromosome 21 affects NCC during development and leads to phenotypes associated with Down syndrome. The deficits caused by trisomy may involve the generation, migration, proliferation, or differentiation of NCC. Using mouse models and in vitro culture systems we want to understand the cellular, genetic, and molecular mechanisms leading to trisomic NCC deficiencies, and identify temporally and spatially specific points for intervention. The long range goal of our work is to discover a molecular therapy to prevent or correct neural crest-related abnormalities in individuals with trisomy.

Recent Publications

  • Roper, RJ, Reeves, RH. Understanding the basis for Down syndrome phenotypes. PLoS Genet. 2006 Mar;2(3):e50.
  • Roper, RJ, Baxter, LL, Saran, NG, Klinedinst, DK, Beachy, PA, Reeves, RH. Defective cerebellar response to mitogenic Hedgehog signaling in Down syndrome mice.
  • Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1452-6. Epub 2006 Jan 23.
  • Roper, RJ, St John, HK, Philip, J, Lawler, A, Reeves, RH. Perinatal loss of Ts65Dn Down syndrome mice. Genetics. 2006 Jan;172(1):437-43. Epub 2005 Sep 19.
  • Olson LE, Roper RJ, Baxter LL, Carlson EJ, Epstein CJ, Reeves RH. Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes. Dev Dyn. 2004 Jul;230(3):581-9.

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Rosamund C. Smith, PhD

Rosamund C. Smith
  • Research Advisor, Biotechnology Discovery Research
  • Adjunct Professor, Dept. of Biology, IUPUI

Lilly Research Laboratories DC 0434
Lilly Corporate Center
Indianapolis, IN 46285

Phone: (317) 277-5229
Fax: (317) 277-2934
Email: smith_ros@lilly.com

Research Interests

My research group is part of the Biotechnology Discovery Research division of Lilly Research Laboratories, a division of Eli Lilly and Company. Our goal is to develop new pharmaceuticals for the treatment of human disease. I am particularly interested in developing novel therapies that will aid human tissue regeneration and repair. We (in collaboration with the IU Center for Regenerative Biology and Medicine, Indianapolis, IN, USA) have used the frog Xenopus laevis to identify genes that are involved in limb regeneration. A number of these genes have mammalian homologues and we are currently exploring the role and potential therapeutic utility of these genes in mammalian tissue repair.

Recent Publications

  • Smith R.C. and Rhodes S. (2000) Applications of developmental biology to medicine and animal agriculture. Progress in Drug Research 54, 214-256.
  • Chernoff E.A.G., Clarke D.O., Wallace-Evers. J.L., Hungate-Muegge L.P. and R.C. Smith (2001) The effect of collagen synthesis inhibitory drugs on somitogenesis and myogenin expression in cultured chick and mouse embryos. Tissue and Cell, 33, 97-110.
  • Krishnan P., King M.W., Neff A.W., Sandusky G.E., Bierman K.L., Grinnell B., and Smith R.C. (2001). Human truncated Smad 6 (Smad6s) inhibits the BMP pathway in Xenopus laevis. Develop. Growth Differ. 43, 115-132.
  • King M.W., Nguyen T., Calley J., Harty M.W., Muzinich M.C., Mescher A.L., Chalfant C., N’Cho M., McLeaster K., McEntire J., Stocum D., Smith R.C. and Neff A. W. (2003) Identification of genes expressed during Xenopus laevis limb regeneration by using subtractive hybridization. Dev. Dynamics 226, 398-409
  • Neff A.W., King M.W., Harty M.W., Nguyen T., Calley J., Smith R.C. .and Mescher A.L. (2005) Expression of Xenopus XlSALL4 during limb development and regeneration. Dev. Dynamics 233, 356-367.

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Fengyu Song, DDS, MS, PhD

Fengyu Song
  • Assistant Professor

Indiana University School of Dentistry
Department of Oral Biology
1121 W. Michigan Street, Room 244
Indianapolis, Indiana 46202

Phone: (317) 274-2415
Fax: (317) 278-1411
Email: fesong@iupui.edu

Research Interests

The research in my laboratory has been focused on the extracellular matrix (ECM) turnover in healthy and diseased tissues, and in the tissue regeneration process. ECM proteinases, including serine proteinases, cystein proteinases, and a group of zinc-dependent endopeptidases known as the matrix metalloproteinases (MMPs), collectively are capable of cleaving most of the major components of the ECM and are believed to be some of the tools by which cells facilitate the ECM remodeling during the degeneration and regeneration process. Specifically we are examining:

  • The roles of the serine proteinases and MMPs in the degenerative joint diseases including temporamandibular joint disorder, osteoarthritis, and rheumatoid arthritis to seek the potential marker(s) for disease diagnosis and treatment;
  • The roles of MMPs in amphibian limb regeneration using regeneration capable and incapable animal models such as the frog Xenopus laevis, and the axolotl, Ambystoma mexicanum; and
  • The induction of the regenerative ability of adult stem cells, including pulp stem cells and gingival fibroblasts, in order to restore the abilities of these cells to regenerate the tooth, the gingival soft tissue and the periodontal bone.

Recent Publications

  • Song F, Windsor LJ (2005) Novel non-matrix metalloproteinase mediated collagen degradation. Biochimica et Biophysica Acta (BBA) - General Subjects, 1721(1): 65-72.
  • Song F, Wisithprom K, Zhou J, Windsor LJ (2006) Matrix metalloproteinase dependent and independent collagen degradation. Frontiers in Bioscience, 11:3100-20.
  • Song F, Bergdoll AS, Windsor LJ (2006) Temporomandibular joint synovial fibroblasts mediate serine proteinase dependent Type I collagen degradation. Biochimica et Biophysica Acta (BBA) - General Subjects, 1760 (10): 1521-1528.
  • Ellis M, Song F, Parks ET, Eckert G, Dean J, Windsor LJ (2007) An Evaluation of Toothprints®: DNA yield, quality, and bite registration. J Am Dent Assoc, 138(9):1234-1240.

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David L. Stocum, PhD

David L. Stocum
  • Professor of Biology
  • Director, Indiana University Center for Regenerative Biology and Medicine
  • Research Scholar, Institute for Genomic Biology, University of Illinois at Urbana-Champaign

Department of Biology, School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan St.
Indianapolis, IN 46204

Phone: (317) 274-0627
Fax: (317) 274-2846
Email: dstocum@iupui.edu

Research Interests

Research in my laboratory has three foci. The first is the cellular and molecular analysis of how the amphibian limb regeneration blastema self-organizes the patterning of amputated limb segments in the proximodistal axis. The second is proteomic analysis of the molecular differences that differentiate the regeneration-competent limbs of salamanders and early frog tadpoles from the regeneration-deficient limbs of metamorphosed froglets. The third is the use of regeneration templates that mimic the ECM, as well as signaling molecules, of regeneration-competent limbs, to investigate ways to promote the regeneration of regeneration-deficient froglet limbs and mouse digits. In addition, I write articles and books that synthesize and promote the rapidly emerging field of regenerative biology and medicine.

Recent Publications

  • Stocum DL (2003) Stem cells in amphibian regeneration. In: Stem Cell Handbook. Sell S, ed. Humana Press, Towota, NJ, pp 89-100.
  • Stocum DL (2004) Amphibian regeneration and stem cells. In Regeneration: Beyond the Stem Cells. Heber-Katz E (ed). Springer Verlag, Heidelberg, pp 1-70.
  • Stocum DL (2004) Tissue Restoration Through Regenerative Biology and Medicine. Adv in Anat, Embryol and Cell Biol 176:1-104.
  • Stocum DL (2005) Stem cells in CNS and cardiac regeneration. In: Advances in Biochemical Engineering/Biotechnology: Regenerative Medicine. Yannas IV (ed). Springer-Verlag, pp 135-159.
  • Stocum DL (2006) “Regenerative Biology and Medicine”. Academic Press, San Diego/Elsevier, New York, 435 pp.

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Stephen Trippel, MD

Stephen Trippel
  • Professor of Orthopaedic Surgery

Department of Orthopaedic Surgery
Indiana University School of Medicine
541 Clinical Drive, Suite 600
Indiana University-Purdue University Indianapolis
Indianapolis, IN 46202

Phone: (317) 278-6904
Fax: (317) 274-3702
Email: strippel@iupui.edu

Research Interests

Arthritis is among the principle causes of disability. This disease reflects damage to the articular cartilage surface of joints. The focus of our research is to identify and apply naturally occurring proteins, known as growth factors, to articular cartilage repair. We are taking a multi-disciplinary approach to this problem, with an emphasis on cellular and molecular biological, and gene therapy technologies.

Recent Publications

  • Madry H, Emkey G, Zurakowski D, Trippel SB: 2004 Overexpression of human fibroblast growth factor 2 stimulates all proliferation in an ex vivo model of articular chondrocytes transplantation. J Gene Med. 6: 238-245.
  • Trippel SB: 2004 Growth factor inhibition: Potential role in the etiopathogenesis of osteoarthritis. Clin Orthop. 427S:S47-S52.
  • Madry H, Cucciarini M, Kaul G, Kohn D, Terwilliger EF, Trippel SB: 2004 Menisci are efficiently transduced by recombinant adeno-associated virus vectors in vitro and in vivo. Amer J Sports Med. 32:1860-1865.
  • Cucciarini M, Madry H, Ma C, Thurn T, Zurakowski D, Menger MD, Kohn D, Trippel SB, Terwilliger EF: 2005 Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2. Molecular Therapy 12:229-238
  • Madry H, Kaul G, Cucchiarini M, Stein U, Zurakowski D, Remberger K, Menger MD, Kohn D, Trippel SB: 2005 Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I). Gene Therapy 12:1171-1179.

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Mu Wang, PhD

Mu Wang
  • Assistant Professor of Biochemistry and Molecular Biology
  • Adjunct Assistant Professor of Informatics
  • Director, Protein Analysis Research Center
  • Indiana Centers for Applied Protein Sciences (INCAPS)

Department of Biochemistry and Molecular Biology
Indiana University School of Medicine
Indiana University-Purdue University Indianapolis
Biotechnology Research and Training Center
1345 W. 16th St, Room 312
Indianapolis, IN 46202

Phone: (317) 278-0296; (317) 274-1446 (INCAPS)
Fax: (317) 278-9739
Email: muwang@iupui.edu

Research Interests

1. Molecular Mechanisms of DNA Damage and Repair
Damage to DNA is an important etiologic pathway for a number of important processes such as cancer, birth defects and aging. Therefore understanding DNA repair pathways is very important. One of my research interests is to study DNA repair mechanisms in both normal and repair deficient mammalian cell lines. We have developed a method for monitoring the interactions between DNA repair proteins and damaged DNA using surface plasmon resonance (SPR) technology, and we are able to make DNA containing different types of damage produced by selected mutagenic and carcinogenic agents such as UV and cisplatin. By using DNA substrates containing site specific adducts, we have been able to determine the preference in DNA binding activity for DNA repair proteins on damaged DNA. Understanding the mechanism of DNA repair pathway will help development of gene therapy as well as chemotherapy of the DNA repair-deficient diseases such as xeroderma pigmentosum (XP). In addition, we are also interested in studying Fanconi anemia (FA), a disorder characterized by bone marrow failure and development of leukemia and other malignancies, in which there is a marked hypersensitivity to DNA interstrand cross linking agents. To date, eleven complementation groups (FA-A to FA-L) have been identified. However, the function of each complementing protein remains largely unknown. We are particularly interested in studying the interactions of FA proteins with other DNA repair proteins using both molecular biology and bioanalytic chemistry techniques. With recent advancement of proteomic technologies, mass spectrometry will be the main tool applied for identification of proteins that interact with FA proteins. The goal of our study is to test 1) whether these FA proteins form complex at the damaged site on DNA, either with each other or with other DNA repair proteins, and 2) what is the role of each protein in damage recognition and/or DNA repair processes.

2. Biomarkers for Cisplatin Resistance in Human Tumor Cells using Proteomics
Platinum-based chemotherapy is still the primary treatment for many types of cancer. Most patients with the disease are initially responsive to chemotherapeutic treatment. However, the majority of cancer patients eventually relapse and become refractory to additional treatment. This drug-resistance is a major impediment to the successful treatment of cancer. To date the mechanisms of drug-resistance are poorly understood. Previous studies have suggested that many proteins, such as BRCA1, BRCA2, MDR1, MRP1, MDM2, hMLH1, HSP27, and HSP70, are differentially expressed in drug-resistant tumor cells, such as ovarian tumor cells, by mRNA differential display analysis. However, global protein pattern changes in these tumor cells have not yet been demonstrated. With recent developments in electrophoresis, imaging, and mass spectrometric technologies, along with the explosion in genomic and protein bioinformatics, the complex status of protein expression, defined as “expression” proteomics, can be analyzed. It is possible to examine, at the molecular level, the perturbations of physiological processes, as well as mechanisms of disease, injury, and therapeutic intervention, by profiling the proteins comprising the organellar, cellular, or extracellular proteomes. Proteomics has provided a very important tool to revolutionize disease diagnosis, drug target discovery, and new therapeutic development.

Since there is no established protein expression profile between drug-sensitive and -resistant ovarian cancer cells, we will choose established ovarian cancer cell lines as the model system for our investigation. We will apply the cutting-edge proteomic technologies such as MudPIT and Label-free Protein Quantification to identify novel proteins associated with cisplatin-resistance in human ovarian cancer cells and thus define new therapeutic targets in ovarian cancer intervention. Once new targets are identified by proteomics, we will develop a strategy to modulate the expression of particular proteins, and then evaluate whether this strategy can lead to the reversal of cisplatin sensitivity of the ovarian cancer cells.

Along the way, we will develop a strategy for subcellular fractionation of lysates obtained from ovarian cancer cells in order to increase depth-of-field (protein dynamic range). Application of this strategy will enhance our ability to examine low abundance proteins in the whole cell lysates. Each fraction will be quantitatively analyzed by quantitative mass spectrometry. Our work will provide important information about biomarkers for drug-resistance in ovarian cancer cells. Identification of biomarker(s) for cisplatin-resistance in ovarian cancer cells and modulation of these biomarkers' expression levels will be clinically significant for finding potential therapeutic targets to develop antitumor drugs and control tumor growth.

Recent Publications

  • Cocklin, R. R.; Zhang, Y.; O'Neill, K. D.; Chen, N. X.; Moe, S. M.; Bidasee, K. R.; Wang, M. (2003) Identity and localization of advanced glycation end products on human beta-2-microglobulin using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anal. Biochem. 314, 322-325.
  • Decker, E. D.; Zhang, Y.; Cocklin, R. R.; Witzmann, F. A.; Wang, M. (2003) Proteomic analysis of differential protein expression induced by ultraviolet light radiation in HeLa cells. Proteomics. 3, 2019-2027.
  • Zhang, Y.; Cocklin, R. R.; Bidasee, K.R.; Wang, M. (2003) Rapid determination of advanced-glycation end products of proteins using MALDI-TOF mass spectrometry and PERL script peptide searching algorithm. J. Biomol. Tech. 14, 224-230.
  • Tao, W.; Wang, M.; Voss, E. D.; Cocklin, R. R.; Smith, J. A.; Cooper, S. H.; Broxmeyer, H. E. (2004) Comparative proteomic analysis of human CD34+ stem/progenitor cells and mature CD15+ myeloid cells. Stem Cells. 22, 1003-1014.
  • You, J-S.; Gelfanova, V.; Knierman, M. D.; Witzmann, F. A.; Wang, M.; Hale, J.E. (2005) The impact of blood contamination on the proteome of cerebrospinal fluid. Proteomics. 5, 290-296.

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David D. Weaver, M.S., M.D.

David D. Weaver
  • Professor Emeritus, Department of Medical and Molecular Genetics

Indiana University School of Medicine
975 W. Walnut Street
Indianapolis, Indiana 46202-5251

Phone: (317) 274-5740
Email: dweaver@iupui.edu

David Weaver is a clinical geneticist with primary interests in dysmorphology and the mechanisms causing birth defects at the gastrulation stage of development. Dr. Weaver earned both an MD and MS in Anatomy at the Oregon Health and Science University, graduating in 1966. Following a general rotating internship in the Milwaukee County General Hospital in Milwaukee, Wisconsin, he spent three years doing research on inherited biochemical defects among the Alaskan Eskimos at the US Public Health Service’s Arctic Health Research Center in Fairbanks, Alaska. After a Pediatric Residency at the Oregon Health and Science University, he did a Human Genetics Fellowship in the Division of Human Genetics at the University of Washington School of Medicine working on X inactivation and dysmorphology. Dr. Weaver then took a second fellowship in metabolism at the Oregon Health and Science University before joined the faculty in the Department of Medical and Molecular Genetics at Indiana University School of Medicine in Indianapolis. Dr. Weaver has published widely in the area of dysmorphology, and has described a number of new dysmorphic syndromes and proposed several new mechanisms producing dysmorphic conditions.

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L. Jack Windsor, Ph.D.

L. Jack Windsor, Ph.D.
  • Associate Professor, Department of Oral Biology, School of Dentistry
  • Adjunct Associate Professor, Department of Anatomy and Cell Biology, School of Medicine

Indiana University School of Dentistry
Department of Oral Biology
1121 W. Michigan Street, Room, DS 271
Indianapolis, IN 46202-5186

Phone: (317) 274-1448
Fax: (317)278-1411
E-mail: ljwindso@iupui.edu

Research Interests

The research focus of the laboratory is on the mechanisms by which extracellular matrix (ECM) is remodeled and/or degraded during normal and pathological conditions. The major players in these processes are the matrix metalloproteinases, which are zinc-dependent proteases that cleave multiple components of the ECM. These proteases are also believed to play major roles during growth and development, as well as during the regeneration process. Some of the laboratory’s efforts have been on understanding how the process of ECM turnover can be regulated to enhance tissue regeneration in the oral cavity such as re-establishment (regeneration) of gingival tissues after periodontal disease, as well as the regulation of pulp stem cells and pulp fibroblasts in regards to the regeneration of tooth structure and possible teeth. In addition, the effects that dental materials and environmental factors (i.e., tobacco) have on the repair/regeneration mechanisms of oral and pulp tissues are being examined.

Recent Publications

  • Song, F. and Windsor, L. J.: Non-Matrix Metalloproteinases (MMP) Mediated Collagen Degradation, Biochim. Biophys. Acta, 1721:65-72, 2005.
  • Zhou, J. and Windsor, L. J.: Porphyromonas gingivalis affects Host Collagen Degradation by Affecting Expression, Activation, and Inhibition of Matrix Metalloproteinases, J. Periodont. Res., 41:47-54, 2006.
  • Wisithphrom, K. and Windsor, L. J.: Interleukin-1a Alters the Expression of Matrix Metalloproteinases and the Collagen Degradation by Pulp Fibroblasts, J. Endod., 32:186-192, 2006.
  • Wisithphrom, K., Murray, P. E., About, I. A., Franquin, J-C., and Windsor, L. J.: The effect of the interactions between cavity preparation and restoration events and their effects on pulp vitality, Int. J. Peridontics Restorative Dent., 26:596-605, 2006.
  • Song, F., Wisithphrom, K., Zhou, J., and Windsor, L. J.: Matrix Metalloproteinase Dependent and Independent Collagen Degradation, Front. Biosci., 11:3100-3120, 2006.
  • Wisithphrom, K. and Windsor, L. J.: The Effects of Tumor Necrosis Factor-α, Interleukin-1β, Interlukin-6, and Transforming Growth Factor-β1 on Pulp Fibroblast Mediated Collagen Degradation, J. Endod., 32:853-861, 2006.
  • Song, F., Bergdoll, A. S., and Windsor, L. J.: Temporomandibular Joint Synovial Fibroblasts Mediate Serine proteinase Dependent Type 1 Collagen Degradation, Biochim. Biophys. Acta, 1760:1521-1528, 2006.
  • Zhou, J. and Windsor, L. J.: Heterogeneity in the Collagen Degrading Ability of Porphyromas gingivalis Stimulated Human Gingival Fibroblasts, J. Periodont. Res., 42:77-84, 2007.
  • Zhou, J., Olson, B. L., and Windsor, L. J.: Nicotine Increases the Collagen Degrading Ability of Human Gingival Fibroblasts, J. Periodont. Res., 42:228-235, 2007.
  • Ellis, M., Song, F., Parks, E. T., Eckert, G. J., Dean, J. A., and Windsor, L. J.: An Evaluation of Toothprints® for DNA Yield, DNA Quality, and Bite Registration, JADA, 138:1234-1240, 2007.
  • Almasri, A., Wisithphrom, K., Windsor, L. J., and Olson, B. L.: Effects of Nicotine and Lipopolysaccharide on Cytokine Expression by Gingival Fibroblasts, J. Periodontol, 78:533-541, 2007.
  • Chen, Y., Zhang, W., Geng, N., Tian, K., and Windsor, L. J.: Role of MMPs, TIMPs, and TGF-beta1 in the cancerization of oral lichen planus, J. Oral Pathol Med, submitted, 2007.
  • Al-Shibani, N., and Windsor, L. J.: Effects of Porphyromonas on gingival fibroblasts from healthy and inflamed tissues, J. Periodont. Res., in press, 2008.
  • Gregson, K., O’Neill, J. T., Platt, J. A., and Windsor, L. J.: Induction of hydrolytic activity by triethylene glycol dimethacrylate and monocyte chemotatic protein-1, Dent. Mater., in press, 2007.

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Feng C. Zhou, PhD

Feng C. Zhou
  • Professor of Anatomy, Cell Biology and Neurobiology, Stark Neuroscience Research Institute

Department of Anatomy and Cell Biology
MS 508
Indiana University School of Medicine
Indiana University-Purdue University Indianapolis
635 Barnhill Drive
Indianapolis, IN 46202

Phone: (317) 274-7359
Fax: (317) 274-3912
E-mail: imce100@iupui.edu

Research Interests

The research theme in my laboratory is Neuroadaptation which includes: Neurobiology of substance abuse and neurodevelopmental and neurodegenerative disorders. The neural system as a whole has an intricate (re)molding ability: environmental impact has the potential to alter gene expression or epigenetic modification, to reprogram neurodevelopmental sequence and pathway, and to modify adult functional pathways and synaptic & receptor plasticity. These (re)molding abilities are collectively called Neuroadaptation. It is neuroadaptation that may underlie the mechanisms of substance abuse, altered state of mind, and neurodegenerative / neurodevelopmental disorders.

Fetal Alcohol Syndrome: Women drinking during pregnancy give birth to children with growth retardation, neural development deficit, and facial dysmorphology know as fetal alcohol syndrome (FAS). We are interested in studying deficits resulting from FAS, including serotonin and sensory cortical systems, mechanism via epigenetic and developmental gene (bHLH, neurogenin and NKX2.2) alteration, and treatment using neurotrophic peptides.

Alcohol Abuse and Synaptic Adaptation: Repeated high alcohol intake induces neuroadaptation. We investigate how chronic alcohol exposure alters the brain into an “addictive” state using two-photon microscopy to monitor presynaptic glutamate and dopamine terminals and postsynaptic NMDA, AMPA, mGluR receptors on dendritic spines in the reward circuitry.

Neural Stem Cells and Neurodegenerative Disease: We are interested in injury spinal cord injury and Parkinsonism and their treatment using embryonic stem (ES) and adult neural stem cells, and molecular genetic approaches.

Recent Publications

  • Zhou, F.C. and R. P. Singh (2003) Regulation of neural stem cells in the adult mammalian brain, In Neuronal and Vascular Plasticity: Elucidating Basic Cellular Mechanisms for Future Therapeutic Discovery. Chap 9. P219-256. Kluwer Academic Publishers. New York
  • Powrozek, TA, Sari, Y. Singh, RP, and F.C. Zhou. Neurotransmitters and drugs of abuse: effects on adult neurogenesis, Current Neurovascular Res. 1 (2004)252-260
  • Ogawa T, Kuwagata M, Ruiz J, and Zhou F.C. (2005) Differential teratogenic effect of alcohol on embryonic development between C57BL/6 and DBA/2 Mice: A new view. Alcohol Clin Exp Res., 29:855-63.
  • Zhou F.C., Sari, Y, Powrozek T, and Spong CY. A neuroprotective peptide antagonizes fetal alcohol exposure compromised brain growth. J. Mole. Neurosci, 24(2004)189-199.
  • Chiang YH, Lin SZ, Zhou F.C. Bridging nigrostriatal pathway with fibroblast growth factor-primed peripheral nerves and fetal ventral mesencephalon transplant recuperates from deficits in parkinsonian rats. Cell Transplant. 2006;15(6):475-82

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Administrative Location and Contact

Department of Biology, School of Science
Indiana University-Purdue University Indianapolis (IUPUI)
SL 306, 723 West Michigan Street
Indianapolis, IN 46202-5191

IUPUIDr. David L. Stocum, Director
Tel: (317) 274-0627
dstocum@iupui.edu