Uniformed Services University of the Health Sciences Report description of the institution, such as history and organization of the laboratory, such as his

Uniformed Services University of the Health Sciences Report description of the institution, such as history and organization of the laboratory, such as history, organization, and personnel and their research projects.

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Uniformed Services University of the Health Sciences

Department of Pathology

Dr. Mary Lou Cutler


Research Interests

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https://www.usuhs.edu/faculty-staff/mary-lou-cutle… 1 Introduction
1.1 Uniformed Services University of the Health Sciences
It is a health science university which is a federal government of the United States. The
mission of the Uniformed Services University of the Health Sciences is to educate the
uniformed services health professionals, National Security and leaders to support the
Military, scientists ,Public Health Systems, and National Defense Strategies of the United
States.Where is located in Bethesda, Maryland. 1972 established the Uniformed Services
University under legislation representative Felix Edward Hébert of Louisiana by United State.
The First class graduated in 1980. The Uniformed Services University of the Health Sciences
which are consists various approaches of Health Professions Education. The F. Edward
Hébert School of Medicine is a health sciences graduate education program doctorate and
master’s degrees in public health and related disciplines such as doctorate degrees in
medicine and medical clinical psychology, and interdisciplinary Ph.D. degrees in three
military-relevant areas of science include cell biology,molecular and, neuroscience and
emerging infectious diseases medical school. The Daniel K. Inouye Graduate School of
Nursing offers a Master of Science in Nursing and a Doctor of Nursing Practice in AdultGerontology Clinical Nurse Specialist. Ph.D. in Nursing Science, Doctor of Nursing Practice in
Nurse Anesthesia, Women’s Health Nurse, Family Nurse Practitioner, and Psychiatric
Mental Health Nurse Practitioner. The Uniformed Services University of the Health Sciences
are unique in relating military medicine, disaster medicine, and military medical readiness
to the uniformed services and the Nation ,as an outstanding academic health sciences
1.2 Department of Pathology
It was established in 1976 under the direction of Kenneth Earle, M.D. The mission of the
Department is to prepare medical students for their clinical life and learn about human
diseases to develop which is a help to understand the disease processes to diagnosis, and
treatment of the patients. The students will understand the origin and symptoms of the
disease, and how the pathology expertise and promote the military readiness delivering the
highest quality of evidence based on the laboratory to support diagnoses the patients. , and
develop the research and disseminate the new knowledge to advance medical science and
military medicine. The research is an essential of their mission for the pathology
department, they focusing on programs to define the pathogenesis of human diseases which
affect both military and civilians. It includes cancer biology, vaccine development,
immunopathology, and human immunity, radiation biology, vector-borne infectious
diseases, and mechanisms of radioresistance, neuropathology of traumatic brain.
Department faculty instructs the graduate students to advanced courses which are
laboratory rotations, and intensive laboratory to achieve doctoral degrees in Molecular and
Cell Biology. The pathologist’s faculty also function as practitioners of Anatomic and Clinical
Pathology at other medical treatment facilities across the National Capital Region.
2 Dr. Mary Lou Cutler
2.1 Biography
Dr. Mary Lou Cutler is the Director of the Molecular and Cellular Biology for Graduate
Program and the Professor of Primary Appointment Department of Pathology and the at
the Uniformed Services University of the Health Sciences in Bethesda, Maryland. In 1974 she
received her bachelor Biology, from Lehigh University, Bethlehem. 1978 received her
Masters of Science in Microbiology and Immunology and in 1980 Ph.D. in Microbiology and
Immunology from Drexel University School of Medicine. Dr. Cutler completed Post-doctoral
Fellow, Laboratory of Molecular Oncology, NCI, NIH in Bethesda 1980 to 1983. Following for
her experience she worked in industry and as an investigator in the Laboratory of Tumor
Immunology and Biology at the NCI prior to joining USUHS. Dr. Cutler worked as a
representative of USUHS to the Murtha Cancer Center at Walter Reed National Military
Medical Center.
2.2 Research Interests
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.
The contributions of the transforming growth factors, oncogenes and tumor suppressor
genes to the malignant transformation of cells and the loss of differentiated cell functions.
Ongoing projects include the study of Rsu-1, the Ras suppressor molecule, the mechanisms
by which it regulates tumor cell adhesion and the role of adhesion in the response of tumor
cells to chemotherapeutic agents. The other area of research in my lab focuses on the
control of mammary epithelial cell differentiation during development.
Rsu1 was identified based on its property of specifically suppressing Ras transformation in
both fibroblasts and epithelial cells. The defining elements of the Rsu-1 protein are a series
of amphipathic leucine-based repeats, referred to as leucine-rich repeats or LRR which bind
to the adaptor protein PINCH1 (Dougherty et al. 2005, 2008). A complex of parvin-integrin
linked kinase (ILK)-PINCH1-Rsu-1 participates in cell adhesion by linking beta subunits of
integrin to the actin cytoskeleton. The knockdown of any of these proteins in cell culture
results in loss of cell adhesion.
Ectopic Rsu-1 expression prevents both oncogenic growth of specific human glial and breast
tumor cell lines and tumor formation in a nude mouse model. Screening human tumors for
RSU-1 loss and mutation revealed that glial tumors frequently expressed an altered spliced
product of the RSU-1 gene. This RNA is missing a single exon and encodes an Rsu-1 protein
lacking the COOH terminus (Chunduru et al. 2002). Alternative splicing of Rsu-1 in human
tumor cell lines is dependent on activation of Ras pathway (Dougherty et al., 2008) and
studies examining the regulatory function of the alternatively spliced RNA in breast and glial
tumors are ongoing in the lab.
The impact of tumor cell adhesion on the response of solid tumors to chemotherapy is an
application of our work on the parvin-ILK-PINCH1-Rsu-1 complex and we are pursuing this
project in collaboration with Dr. Peter D’Arpa, an expert on topoisomerase function.
The regulation of mammary epithelial cell differentiation.
Epidemiological evidence indicates that early pregnancy and lactogenic differentiation can
reduce the risk of both pre- and post-menopausal breast carcinoma. Hence, a complete
understanding of the regulation of mammary differentiation is important in elucidating the
mechanisms leading to breast carcinogenesis. Global expression profiling of mammary
epithelial cells undergoing lactogenic differentiation identified the matricellular protein
connective tissue growth factor (CTGF/CCN2) as highly up regulated during lactogenic
differentiation and that CTGF/CCN2 binding to ?1 integrin is required for differentiation
(Wang et al. 2007 and Morrison et al. 2010). The potential application of this work to human
breast cancer is significant because the molecular signature of genes transcriptionally
activated during differentiation includes a number of transcripts that are found at high levels
in breast tumors that metastasize to bone, a site of CTGF/CCN2 expression. Hence, the
results of our analysis of differentiating mammary epithelial cells may help define elements
of transcriptional control that are important for tumor progression in this tissue.

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