Click on the faculty member’s name for a more in-depth description of their research and publications.
DEPARTMENT OF BIOCHEMISTRY AND CANCER BIOLOGY
Ivana de la Serna, Ph.D.
Assistant Professor
University Of California, Davis, 1998
In eukaryotes, DNA is packaged into chromatin, the basic unit of which is the nucleosome. Chromatin structure plays a critical role in the regulation of gene expression by imposing topological constraints and by creating a barrier for general transcription factors and other regulators. Dr. de la Serna studies the functional role of mammalian SWI/SNF chromatin-remodeling enzymes and their effects on muscle and melanocyte differentiation.
Kathryn Eisenmann, Ph.D.
Assistant Professor
University of Minnesota, Twin Cities, 2000
Understanding the role of Dia-interacting protein (DIP) in controlling formin (de)activation and its affects on amoeboid cell movement that may lend novel insight as to mechanisms controlling the transition towards amoeboid-based cell migration/invasion and metastasis of breast cancer cells and provide aan alternate therapeutic avenue.
J. David Dignam, Ph.D.
Professor
University of Texas, Houston, 1977
Dr. Dignam studies various aspects of nucleic acid enzymology focusing on with the structure and function of aminoacyl-tRNA synthetases which are essential for protein translation and the helicase proteins of adeno-associated virus.
William A. Maltese, Ph.D.Professor and Chairman
Syracuse University, Syracuse, NY, 1977
Dr. Maltese’s laboratory studies the Ras-related GTP-binding proteins encoded by the Rab gene family in mammalian cells. Rab proteins are localized in discrete organelles and vesicles, where they play key roles in protein trafficking between specific donor and acceptor compartments along the exocytic or endocytic routes. Rab proteins function in pathways that are required for cell growth, tumor metastasis, posttranslational processing of cell surface glycoproteins, and secretion of biologically important peptides.
Maurice Manning, Ph.D., D.Sc.
Professor
University of London, London, England, 1961
Research in Dr. Manning’s laboratory is focused on the design and solid phase synthesis of selective agonists and antagonists for the known (V1a, V1b, V2 and OT) receptors of the neurohypophysial hormones vasopressin and oxytocin.
Jean H. Overmeyer, Ph.D.
Research Associate Professor
University of Kentucky, Lexington, KY, 1991
I have been studying the mechanisms of Ras-induced cell death in glioblastoma cells. Activated HRas(G12V) is commonly found in many types of human cancers, but conspicuously missing from others. Glioblastomas are one of the tumor types where HRas(G12V) is rarely found. We and others have observed that expression of this activated form of HRas in glioblastoma cell lines leads to an extensive accumulation of cytoplasmic vacuoles, culminating in cell death. However, the cell death pathway that is induced under these conditions appears to be distinct from the well-defined mechanisms of classical apoptosis. The observations that the HRas(G12V)-induced vacuoles are not acidic, the surrounding membrane frequently contains Lamp1, a lysosomal marker, and the formation of the vacuoles coincides with the induction of processing of an autophagic marker, LC3-I to LC3-II, initially led us to believe the cells may be undergoing Type II cell death, also known as autophagy. However, upon closer examination, we have found that despite the observed increase in endogenous autophagy, as indicated by the increase in LC3-II production, the HRas(G12V)-induced vacuoles themselves do not appear to be autophagic in nature, as determined by a number of unique characteristics. The HRas(G12V)-induced vacuoles are extremely enlarged relative to normal autophagic vacuoles; they are not surrounded by a double membrane, do not contain cellular organelles and do not sequester LC-II on their membrane. Our studies also indicate that the phase-lucent vacuoles are separate from compartments derived from the ER. In fact, the vacuoles have recently been identified as macropinosomes, as evidenced by the uptake of fluid-phase markers.
I am currently working on identifying the mechanisms that link H-Ras activation to the formation of these macropinosomes. I have shown that activation of other small GTPases, RhoA and Cdc42, do not lead to this mechanism of cell death. However, expression of constitutively active Rac1 is capable of mimicking this effect. Additional studies are underway to precisely define the downstream targets of activated Ras/Rac1 that are required to induce formation of macropinosomes that lead to cell death in gliobastomas. Further elucidation of these mechanistic pathways will improve our knowledge of triggers to induce cell death in some types of cancers.|
Stephan M. Patrick, Ph.D.
Assistant Professor
Wright State University, Dayton, OH, 1999
Cisplatin is a chemotherapeutic drug that is used in the treatment of testicular and ovarian cancers, as well as other cancer types. Many chemotherapeutic drugs, including cisplatin, target DNA and inhibit cells from dividing which ultimately leads to cell death. The major focus of Dr. Patrick’s laboratory is to define the mechanisms of how cancer cells respond to cisplatin-induced DNA damage.
Manohar Ratnam, Ph.D.
Professor
Indian Institute of Science, Bangalore, India, 1983
The mammalian folate receptor (FR) is a prominent topic in current literature due to the interest of investigators in multiple disciplines in the biological sciences. The principal focus of the Ratnam is geared towards a substantial and detailed analysis of key phenomena related to the structure, function, and regulation of FR as well as the clinical contexts in which specific FR isoforms may be utilized for diagnostic, prognostic, and therapeutic applications.
Randall J. Ruch, Ph.D.
Associate Professor
Medical University of Ohio, Toledo, 1988
Dr. Ruch’s research is focused on gap junction proteins to determine the role of these intercellular communication proteins in cellular growth regulation and neoplasia. He also studies how carcinogens, toxicants, and oncogenes alter gap junctional intercellular communication.
Cynthia M. Smas, D.Sc.
Associate Professor
Harvard University, Boston, MA, 1994
Work in Dr. Smas’ laboratory addresses gene regulation and cell differentiation using two model systems: 1.) Differentiation of fibroblastic mesenchymal precursor cells to mature adipocytes that occurs in normal development but which may be accelerated in obesity; and 2.) Neuroendocrine differentiation that occurs during the course of prostate cancer and which may support a transition to androgen-independent tumor growth.
James P. Trempe, Ph.D.
Professor
Wright State University, Dayton, OH, 1985
The current primary goal of Dr. Trempe’s laboratory is to characterize the ability of the human parvovirus, adeno-associated virus (AAV), to suppress the transformation of normal cells to an oncogenic phenotype. His laboratory is also studying ways to use AAV as a gene therapy vector for the treatment of hereditary and acquired human diseases.
Robert J. Trumbly, Ph.D.
Professor
University of California, Davis, CA, 1980
Dr. Trumbly’s major research interest is the mechanism of repression of transcription by the Cyc8-Tup1 complex in the yeast Saccharomyces cerevisiae. The Cyc8-Tup1 complex acts as a co-repressor, which is recruited to different promoters by interaction with several distinct repressor proteins that bind directly to DNA.
Kandace J. Williams, Ph.D.
Professor
Dartmouth Medical School, Hanover, NH, 1987
The discovery of mutational hot spots in the genomes of living organisms has captured the interest of several different scientific disciplines. Because of the strong association between specific mutagenic events and neoplastic transformation, Dr. Williams’ laboratory is interested in learning the molecular mechanisms responsible for increased frequency of mutation at targeted genomic locations.
Kam C. Yeung, Ph.D.
Assistant Professor
University of South Alabama, Mobile, AL, 1990
Dr. Yeung’s laboratory studies the molecular basis of signal transduction and how extracellular signals are transduced into the transcription machinery. During the last few years, his major research activities have been directed at de-convoluting the complex Raf/MEK/Erk signaling pathway. He also studies the general transcription repressor, Dr1/DRAP1, and how its activity is regulated by signaling pathways.
DEPARTMENT OF MEDICAL MICROBIOLOGY AND IMMUNOLOGY
Akira Takashima, M.D., Ph.D.
Professor and Chairman
Nagoya City University Medical School, Nagoya, Japan, 1981 M.D. and 1989 Ph.D.
Dr. Takashima's major research interest is in the immuno-biology of specific leukocyte subsets known as dendritic cells (DCs), which play crucial roles in the induction of both innate and adaptive immunity. The objectives in his laboratory are: (a) to study molecular mechanisms regulating the function of DCs (Basic Immunology), and (b) to develop novel DC-targeted immunotherapeutic (Applied Immunology). For the first objective, Dr. Takashima's group recently developed an intravital confocal imaging system that enables real-time visualization of dynamic 3D behaviors of DCs in living animals. To achieve the second objective, his group established a DC-based biosensor system as a high-throughput drug screening platform for the discovery of agents that deliver DC activation signals. Not only will these ongoing studies provide important insights into the mechanisms controlling the behaviors and functions of DCs under physiological and pathological conditions, they may also lead to the development of innovative therapeutic strategies for the prevention and treatment of cancer, infectious disease, autoimmune disorders, and organ transplantation.
DEPARTMENT OF MEDICINE
Khew-Voon Chin, Ph.D.
Associate Professor
Rutgers University, New Jersey, 1988
Dr. Chin’s laboratory has three areas of research focus: (i) They are interested in novel cAMP signaling mechanisms involving the regulatory subunit (R) of the cAMP dependent protein kinase (PKA). They have shown that the R subunit can interact with novel protein partners and regulate cell growth. (ii) They apply expression genomics (expression profiling by DNA microarray) for the identification of genes that contribute to drug resistance in cancer treatment. (iii) They are also studying the transcriptional regulation of adipogenesis and the molecular actions of a novel small molecule that disrupts this pathway and thus inhibition of fat cells differentiation.
James C. Willey, M.D.Dr. Willey’s laboratory studies the expression of multiple genes simultaneously by quantitative, competitive RT-PCR in normal and tumor respiratory epithelial and alveolar macrophage cells. These studies have provided a molecular signature that allows for a prediction of how aggressive a tumor may become.
DEPARTMENT OF NEUROSCIENCES
Marthe J. Howard, Ph.D.
Professor
University of California, Irvine, CA, 1984
The work in my laboratory focuses on growth and transcription factor regulation in the specification and differentiation of autonomic neurons. We use modern molecular biology and cell biology techniques to assess gene regulation in avian and mouse embryos. The overall goal of our studies is: (1) to identify genetic regulatory networks involved in neurogenesis and expression of neurotransmitter molecules, (2) to identify cell extrinsic signaling molecules involved in neurogenesis, and (3) to understand the interplay between cell extrinsic cues and cell intrinsic patterns of gene regulation resulting in differentiation of autonomic neurons. Howard's lab is funded by the National Institute of Health (NIDDK, NINDS).
DEPARTMENT OF PATHOLOGY
William T. Gunning III, Ph.D.
Professor
Medical University of Ohio, Toledo, OH, 1991
Dr. Gunning’s research is focused on two distinct research projects. One project involves experimental carcinogenesis and chemoprevention studies with the strain A mouse lung tumor adenoma model. The second research project is clinically oriented; it is directed toward evaluation of individuals having prolonged bleeding times.
Ronald Mellgren, Ph.D.
Professor
Iowa State University, Ames, IA, 1976
Eukaryotic cell cycle regulation, regulated intracellular proteolysis.
Virtually all cells derived from multicellular animals possess calpains, non-lysosomal calcium-dependent proteases which participate in the regulated degradation of intracellular proteins. Studies in my laboratory have focused on establishing the physiologic roles of these enzymes, and assessing their potential to produce cell damage in the many pathologic situations known to involve increases in intracellular calcium concentration. Because of the irreversible nature of proteolysis, regulatory intracellular proteases would be expected to control unidirectional processes involving highly committed steps. A good example of this type of process is progression through the cell cycle. Regulated degradation of cyclins and other cycle-specific proteins has emerged as an important mechanism governing passage from one phase of the cell cycle to the next. We are currently studying the role of calpains in cycle-specific proteolysis.
Sonia Najjar, Ph.D.
Professor
Stanford University, Redwood City, CA, 1989
Understanding the mechanisms of obesity, type 2 diabetes and fatty liver disease.
Sumudra Periyasamy, Ph.D.
Assistant Professor
Medical College of Ohio, Toledo, OH, 1988
My research is focused on the molecular biology of prostate cancer, specifically to understand the role of tetratricopeptide repeat (TPR) proteins and their ligands in androgen receptor signaling in prostate cancer. The FK506-binding proteins (FKBP52, FKBP51, PP5) and the cyclosporine A (CsA)-binding protein (Cyp40) are TPR proteins that have been shown to form a heterocomplex with androgen receptor (AR) in prostate cancer cells. With the exception of FKBP51 which is known to be over-expressed in the androgen refractory prostate tumor and a positive regulator of AR, almost nothing is known about how these proteins influence AR functions in prostate cancer. Specifically, we are interested in answering the key question, “Do TPR proteins play a role in initiation and progression of prostate cancer”? To this end, using FKBP52 knockout mice we have recently shown that FKBP52 is essential to AR activity in prostate growth. We have also shown that expression levels of the TPR proteins were higher in prostate cancer cell lines compared to normal epithelial cells. Furthermore, TPR ligands FK506 and CsA inhibited androgen-dependent stimulation of cancer cell growth and gene transcription suggesting that TPR proteins may contribute to the etiology of prostate cancer. Our findings are the first evidence that FK506 and CsA can negatively modulate androgen-dependent functions in prostate cells, and that TPR proteins function as positive regulators of AR-mediated cell growth and gene transcription –providing a potential new strategy for the treatment of prostate cancer.
Edwin R. Sanchez, Ph.D.
Professor
University of Michigan, Ann Arbor, MI, 1983
Regulation of steroid hormone receptors, with emphasis on the convergence of the heat shock, immunophilin and glucocorticoid receptor signal pathways.
DEPARTMENT OF SURGERY
David C. Allison, M.D., Ph.D.
Professor
University of Michigan College of Medicine, Ann Arbor, MI, M.D.
University of Chicago, Chicago, IL, Ph.D.
Dr. Allison’s laboratory is studying the mechanisms responsible for the selection of chromosomal abnormalities in aneuploid cancers. We are specifically testing the possibility that chromosomal abnormalities are conserved to retain cell-survival genes required for tumor-cell growth coincident with the loss of chromosomal regions containing tumor suppressor genes retarding tumor growth, or losses of heterozygosity (LOHs). Special attention is being paid to the possibility that tumor LOHs might prove to be an important indicator for breast cancer patients. Techniques employed in the laboratory include Gene Mapping and Expression Arrays, Spectral Karyotyping analysis of cancer chromosomes, and Laser Capture Microdissection of breast cancer cells in paraffin-embedded tissue blocks.
Keith Crist, M.D.
Associate Professor
University of California at Davis, Davis, CA, Ph.D.
Renal cell and ovarian cancers show initial objective response to first line therapy but are associated with high mortality due to recurrence of chemoresistant disease. Chemosensitization of residual tumor by low dose chemotherapeutic drug treatment followed by IL-2 activation of host cytotoxic immune attack is a possible alternative mode of therapy. We have demonstrated the potential effectiveness of this regimen in an in vitro system and are currently exploring expression differences between control and susceptible drug treated cells. Use of currently approved drugs at low dosage will allow for rapid transition to clinical trials after appropriate pre-clinical work is completed.
Ewa Skrzypczak-Jankun, Ph.D.
Research Associate Professor
A. Mickiewicz University, 1976
(1) Natural compounds and their interaction with enzymes. Utilization of the natural products in the therapy and prevention of diseases. (2) Targeted drug design, molecular modeling with a special emphasis on cancer. (3) Structure and function of enzymes, proteins and natural products. (4) X-ray structural analysis of molecules in single crystals, powders and thin films.