PAT Faculty

1974 B.A., Biology, Lehigh University, Bethlehem, PA 18017
1978 M.S. Microbiology and Immunology, Drexel University School of Medicine, Philadelphia, PA 19102
1980 Ph.D. Microbiology and Immunology, Drexel University School of Medicine, Philadelphia, PA 19102
1980 - 1983 Post-doctoral Fellow, Laboratory of Molecular Oncology, NCI, NIH, Bethesda
Mentor: George F. Vande Woude

Dr. Mary Lou Cutler is Professor in the Department of Pathology and the Director of the Molecular and Cellular Biology Graduate Program at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Maryland. Dr. Cutler serves as a representative of USUHS to the Murtha Cancer Center at Walter Reed National Military Medical Center. She received her PhD in Microbiology from Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Cutler completed post-doctoral studies in the laboratory of Dr. George Vande Woude at the National Cancer Institute (NCI). She worked in industry and as an investigator in the Laboratory of Tumor Immunology and Biology at the NCI prior to joining USUHS.

Her research focuses on the role of cell adhesion molecules in signaling and migration of breast cancer. Dr. Cutler identified molecules that control adhesion and migration through integrins and determined the mechanisms by which they regulate cell stress and susceptibility to oncogenic transformation. Her laboratory identified novel cell adhesion contributions to lactogenesis as well. Dr. Cutler has investigated these basic research questions in the context of cancer development and progression with funding from the National Institutes of Health, the CDMRP Breast Cancer Program and through collaborative research with the Clinical Breast Care Program Center of Excellence at the Murtha Cancer.

After completing a Doctor of Philosophy degree in genetics at Queen Mary, University of London (QMUL), and a post-doctoral fellowship at the National Cancer Institute, Bethesda, MD, Mike Daly joined the Department of Pathology at USU, School of Medicine. Since then, the focus of his research has been the genetic development of the extremely radiation resistant bacterium Deinococcus radiodurans. Early on, it was evident that D. radiodurans is uniquely suited to the analysis of DNA repair, and the goal of his functional genomics-based program has been to harness Deinococcus resistance mechanisms for practical purposes - including bioremediation, radioprotectors, and for preparing irradiated vaccines. This work has been a regular topic of discussion in mainstream academics, biotechnology, on the Internet, Twitter, and in the news media where Deinococcus has been covered by the BBC, The New York Times, The Washington Post, The Economist, and others.

In the early 1990s, based on a rubric for studying DNA recombination in yeast, Daly developed a powerful molecular genetic platform to study ionizing radiation (IR)-induced DNA damage and repair. That platform remains the only study system in which massive genome damage can be interrogated in vivo at exposures commensurate with cellular survival (1. J. Bacteriol. 1996; 178, 4461-4471). This early research was featured by Science magazine (1. Science. 1995; 270, 1318), which led to a collaboration with The Institute for Genomic Research (TIGR), Rockville, MD, yielding two D. radiodurans whole genome sequence (WGS) reports in Science in 1999; the first reporting its mapping, the second reporting its sequence and annotation (2). As few WGS’s were available for comparison back then, Daly’s attentions shifted to showing how the D. radiodurans WGS could be harnessed for practical purposes: Engineering D. radiodurans for metal remediation in radioactive mixed waste environments (3. Nature Biotechnol. 2000; 18, 85-90). This influential bioremediation work revealed that enzymes cloned from IR-sensitive bacteria into D. radiodurans were endowed with extraordinary resistance to IR-induced oxidation; Daly inferred something in Deinococcus cells protected proteins from reactive oxygen species (ROS). In 2001, Daly’s group published the first comprehensive WGS comparative analysis of D. radiodurans, concluding that a genome sequence cannot predict whether a cell is IR-resistant or not (2. Micriobiol. Mol. Biol. Rev. 2001; 65, 44-79). Since then, Daly has led two other Deinococcus WGS projects (D. geothermalis, 2007 and D. ficus, 2017) (2), further strengthening the original conclusion. In 2003, Daly’s group tested their functional predictions by constructing de novo one of the first WGS microarrays for any organism: D. radiodurans (2. PNAS. 2003; 100, 4191-4196). Surprisingly, the transcriptome analysis showed that very few of the novel genes make a significant contribution to the recovery of irradiated D. radiodurans, and that this bacterium relies on a conventional set of DNA repair functions. So, Daly’s focus shifted away from DNA to cell-cleaning functions, and in 2004, he reported the identification of a widespread Mn2+-dependent, nonenzymatic mechanism required for extreme IR resistance (4. Science. 2004; 306, 1025-1028). A founding concept of radiobiology is that IR indiscriminately damages cellular macromolecules. In 2007, Daly et al reported that this classical assumption is wrong: whereas DNA lesion-yields in IR-resistant and IR-sensitive bacteria exposed to a given dose of IR are fixed, protein lesion-yields are highly variable and quantifiably related to survival (4. PLoS Biol. 2007; 5(4), e92). It turned out that protein- and DNA-damage in irradiated cells is readily uncoupled, and that protein protection and IR survival in bacteria is mediated by Mn antioxidant complexes. This iconoclastic view was published by Nature Publishing Group (4. Nat. Rev. Microbiol. 2009; 7, 237-45). Since then, Daly and colleagues have characterized and solved the structure of Deinococcus Mn antioxidants, successfully reconstituting them in the laboratory (4. PloS One. 2010; 5(9), e12570). Such synthetic Deinococcus Mn antioxidants are impressively protective of proteins, not DNA or RNA, and are being used in the development of bacterial and viral vaccines (5. Cell Host Microbe. 2012; 12, 117-124;Vaccine. 2017; 3672-3681); and as in vivo radioprotectors in animals (5. PloS One. 2016; 11(8), e0160575). Most recently, Daly and colleagues have shown that the Mn antioxidant content in non-irradiated living cells is readily gauged by electron paramagnetic resonance (EPR) spectroscopy and is highly diagnostic of their DNA double strand break (DSB) repair efficiency and survival post-irradiation. This spectroscopic measure of cellular Mn content is now the strongest known biological indicator of IR resistance between and within organisms across the three domains of the tree of life, with tangible applications spanning optimization of radiotherapy (5. PNAS. Published October 17, 2017) to the field of astrobiology (6).
Daly’s paradigm-shifting papers have been serving as a ‘Rosetta stone’ in the modern decryption of radiation resistance - away from the many DNA-centric views to one in which a cell’s proteome - not its genome - is the prime target responsible for radiation-induced cell death. This model is known as Death by Protein Damage in Irradiated Cells (4. DNA Repair (Amst.), 2012, 11, 12-21).

A.B. Biology, 1969
Hunter College of City University of New York

POST GRADUATE EDUCATION AND TRAINING:
Ph.D. Pharmacology, 1977
Cornell University Graduate School of Medical Sciences
Sloan-Kettering Division

Postdoctoral Fellow 1977-1981
Department of Cell Biology
The Rockefeller University

My career of over 45 years of scholarly achievement in cancer research, cell biology, cellular neurobiology, parasitology and infectious disease is reflected in 88 peer-reviewed and 127 non-peer-reviewed articles or abstracts of work presented at various scientific meetings worldwide. For the past 15 years my work/interests have focused on understanding the pathophysiology of vascular barrier dysfunction/leakage in the context of infectious diseases. How these relate to traumatic brain injury (TBI) and ionizing radiation are areas for future development. Development of better diagnostics and therapeutics is also another important Research arm. Overall, my global research and teaching experiences will both complement and synergize with programs important to the Department and the military medicine goals of USUHS.

AP/CP Pathology Residency, San Antonio Military Medical Center, San Antonio, TX 2007-2011
Internal Medicine Internship, David Grant Medical Center (DGMC), Travis AFB, CA 2004-2005
D.O., Western University of Health Sciences, Pomona, Ca 2000-2004
M.S. in Biomedical Science, Barry University, Miami, FL 1998-1999
B.A. in Biochemistry & Molecular Biology, University of California, Berkeley, CA 1994-1997

B.A. Columbia College, New York
M.D. State University of New York, Downstate Medical Center
Internship in Pathology, Yale-New Haven Hospital
Resident in Pathology, Yale-New Haven Hospital
Post-Doctoral Fellow in Neuropathology, Department of Pathology, Yale University School of Medicine
American Board of Pathology, Board Certified - Anatomic Pathology, Neuropathology

Dr. Daniel P. Perl was born and raised in New York City and received his BA and MD degrees from Columbia College and the State University of New York. He then took postgraduate training in anatomic pathology and neuropathology at Yale University, following which he served for two years as a pathologist in the US Public Health Service, stationed at the Centers for Disease Control in Atlanta, Georgia. In subsequent years he served on the faculty of the Brown University Medical School and then the University of Vermont College of Medicine. In 1986, Dr. Perl joined the Mount Sinai School of Medicine in New York, where for 24 years he served as Director of the Neuropathology Division and was Professor of Pathology, Psychiatry and Neurosciences.
Dr. Perl is highly regarded for his work on various aspects of the neuropathology of age-related neurodegenerative disorders, especially the role of environmental factors in their induction. He is the leading authority on the pathology of the fascinating complex of neurodegenerative disorders occurring among the native population living on Guam. Prior to coming to Uniformed Services University of the Health Sciences, his research had been continually funded by the National Institutes of Health for 32 years. Dr. Perl has won numerous awards for his research as well as his role as a medical educator.
In September, 2010, Professor Perl left Mount Sinai to join the faculty of the Department of Defense’s Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, in Bethesda, MD. In conjunction with the congressionally mandated Center for Neuroscience and Regenerative Medicine, he has established a state-of-the-art neuropathology laboratory dedicated to research on the acute and long-term effects of traumatic brain injury (TBI) and PTSD among military personnel.

B.S. Brooklyn College (City University of New York), Brooklyn, New York, 1975
M.D. Albany Medical College (Union University, Albany, New York, 1981
Intern, Internal Medicine, Albany Medical Center Hospital, Albany, New York, 1981-1982
Resident, Department of Pathology, The New York Hospital-Cornell Medical Center, New York, New York, 1982-1985
Medical Staff Fellow, Laboratory of Immunology, NIAID, NIH, Bethesda, Maryland, 1985-1988

BS (1994), Chemistry, Statistics, Mathematics, Lucknow University, Lucknow, India

MS (1996), Organic Chemistry, Lucknow University, Lucknow, India,

PhD (2003), Breast Cancer, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (1997-2000); University of Ulm, Ulm, Germany (2000-2002),

Research Fellow, Neurological Diseases, University of Texas Heath Science Center, San Antonio, TX 2002-2003

Research Fellow, Breast Cancer, National Cancer Institute, Bethesda, MD 2003-2004

Research Fellow, Gastrointestinal Cancer, Harvard Medical School, Boston, MA 2004-2007

Research Fellow, Breast Cancer, Georgetown University, Washington, DC 2007-2011

Dr. Geeta Upadhyay is an Assistant Professor in the Department of Pathology and in the Department of Molecular and Cellular Biology at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Maryland. Dr. Upadhyay's laboratory is funded by NCI R01grant and USUHS start up funds. Her research interest is yo develop targeted therapies and understand the mechanistic basis of these therapies in solid cancers such as triple negative breast cancer. Dr. Upadhyay’s lab at USUHS is focused on understanding the role of the Ly6 family of proteins in cancer progression, immune escape and survival outcome. Current projects are focused on understanding the mechanistic basis of Ly6K action on the TGF-beta and tumor immune escape pathways in breast cancer. The novel drug development aspect of the project is focused on testing the small molecule binders of Ly6K in treatment of triple negative breast cancer. Dr. Upadhyay’s lab collaborates with investigators at Clinical Breast Care Program Center of Excellence at John P Murtha Cancer Center at Walter Reed National Military Medical Center, National Cancer of Institute, National Cancer for Advanced Translational Sciences, University of South Carolina, Harvard Medical School and with Georgetown University.

Dr. Upadhyay received award winning PhD degree in 2003 from Molecular Endocrinology of breast cancer at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow. Dr. Upadhyay received her postdoctoral training at Harvard Medical School, Boston; National Institute of Health, Bethesda, University of Texas Health Science Center of San Antonio in the areas of breast, colon cancer and cell signaling pathways of Wnt and oxidative stress pathways. Her postdoctoral work led to identification of a novel regulator DOCK4 in non-canonical Wnt pathway. Dr. Upadhyay served as research faculty at Georgetown University, Washington, DC where she made original observation that stem cell maker Sca-1 binds with TGF-beta receptor-1 in order to disrupt TGF-beta signaling.

BA (cum laude), University of Virginia
MD, University of Virginia
Internship and Junior Residency, Internal Medicine, St. Elizabeth's Hospital (Tufts), Boston, MA
Senior Residency, Internal Medicine, The Carney Hospital (Boston Univ), Boston, MA
Rheumatology Fellowship, Walter Reed Army Med Ctr
Medical Staff Fellow, Experimental Immunology Branch, DCBD, NCI, NIH

Positions and employment
1976-1980 U.S. Army: Internist, Stuttgart, Germany; Asst. Chief Int. Med, West Berlin, Germany
1982-1984 Chief, Rheumatology, Brooke Army Med. Center, San Antonio, TX
1988-2004 Assistant, Associate and Full Professor (with tenure), Univ. Maryland Med. Sch., Chief, Arthritis Clinic, Baltimore VA Hospital. Co-Founder and Director, Maryland Lupus Program.
2004-present Professor, Pathology Dept., Uniformed Services Univ. of Health Sci. Bethesda, MD.

Advisory Committees
Study Sections, full member: NIH: Hypersensitivity, Autoimmune and Immune Diseases (HAI) (2009-2013); Veterans Affairs: Immunology, Merit Review Board (1995-98); Arthritis Foundation: Clinical and Applied Immunology (1991-92), Cellular Immunology (2002-03). DOD: DTRA-TMTI Viral Therapeutics (2006-07). Alliance for Lupus Research: Target Identification in lupus (2005-07, 2009-2013); Lupus Research Inst. (2012-13). NIH ad hoc reviewer: IMS/HAI, IMB, ACTS (1992-2008).
Editorial Boards: Clinical Immunology (1992-2004); Clinical and Diagnostic Laboratory Immunology (2002- 2006), Clinical and Vaccine Immunology (2006-2010), Current Immunol Reviews (2005). Section Editor: The Journal of Immunology (2005-2008), Cellular Immunology (2015-present)
NIAMS Advisory Council, ex officio DOD representative. (2002-2004).

Patents
1996 US Patent # 5,514,556: Method for detecting immune dysfunction in asymptomatic AIDS patients and for predicting organ transplant rejection.GM Shearer, M Clerici, CS Via.