Anatomy, Physiology & Genetics

Matthew D. Wilkerson, Ph.D.

Matt Wilkerson

Name: Matthew D. Wilkerson, Ph.D.

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Director, Informatics Core (CHIRP), Adjunct Associate Professor

Affiliated Center: CHIRP

Links
Lab Website

Profile

The Bioinformatics Core provides computational biology analysis and infrastructure for CHIRP genomic research studies. Our mission is to discover and characterize genomic alterations in patient specimens in order to enable precision medicine, such as characterizing the molecular etiology of disease, predicting disease risk and outcome, and discovering molecular subtypes of disease. We apply and develop computational methods for analyzing high throughput sequencing from the CHIRP sequencing core or from CHIRP affiliated investigators. Bioinformatics Core analysis spans low level analysis to biological hypothesis evaluation and exploration.

The CHIRP Bioinformatics Core is under the direction of Dr. Matthew D. Wilkerson (PubMed). Dr. Wilkerson’s prior academic research has resulted in the discovery of expression subtypes based upon genomewide expression profiles of various cancer types, such as lung adenocarcinoma, lung squamous cell carcinoma, and pheochromocytoma/paraganglioma among others (e.g., Fig 5A). He has published integrated genomic studies that characterized these novel expression subtypes with differential molecular pathogenesis (somatic mutations, germline mutations, copy number alterations, epigenetic alterations), differential patient profiles and environmental exposures, and differential patient survival and chemotherapy response of these molecular subtypes – thus establishing that these expression subtypes are an important classification for precision medicine. In addition, Dr. Wilkerson has developed original computational methods, including methods for identifying somatic mutations in patient-matched DNA and RNA sequencing, for genomic subtype discovery, and for structural comparative genomics. These methods also enable precision medicine, such as identifying actionable mutations in low purity tumors, which has important implications for targeted cancer therapy (e.g. Fig 5).

Schedule a Bioinformatics Core Consultation.

Jeremy Smyth, Ph.D.

Jeremy Smyth

Name: Dr. Jeremy Smyth, Ph.D.

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Assistant Professor

Affiliated Departments: Molecular & Cell Biology, Neuroscience

Email: Jeremy.Smyth@usuhs.edu (link sends e-mail)
Office Phone: (301) 295-5879
Room: C-2123

Links
Department Website
PubMed Listing

Profile

  • Postdoctoral, National Institute of Environmental Health Sciences
  • Ph.D., University of Massachusetts, Amherst, 2004
  • B.A., University of Massachusetts, Amherst, 1999

Research Description

Research in our laboratory focuses on the interface between the morphology and function of the largest organelle in the cell, the endoplasmic reticulum (ER). The ER forms an elaborate, stunningly dynamic network of flat sheets and thin, lattice-like tubules throughout the cytoplasm in animal cells. Defects in ER morphogenesis underlie several debilitating neurodegenerative disorders such as Hereditary Spastic Paraplegia, illustrating the essential role of proper ER morphology in human physiology. However, mechanisms by which specific features of ER morphology and dynamics influence cellular and tissue physiology are still poorly understood. We address this fundamental problem by employing a number of powerful experimental systems, including Drosophila genetics and phenotypic analysis, live microscopy of human and Drosophila cells and tissues, and biochemical assays. We are particularly interested in understanding the functional interactions of the ER with the microtubule cytoskeleton, and are currently pursuing this topic through two related projects:

ER-microtubule interactions during cell division

As for most organelles, cells cannot generate the ER de novo; instead, they must inherit it during the process of cell division. This is not unlike the inheritance and partitioning of chromosomal DNA; however, unlike DNA, the mechanisms that regulate ER distribution and partitioning during cell division are largely unknown. We recently demonstrated that association of the ER with astral microtubules of the mitotic spindle is a conserved mechanism that regulates ER partitioning during both symmetric and asymmetric cell division. Our goal now is to identify the specific molecules that link the ER with spindle microtubules, and using Drosophila as an animal model, to further define the physiological role of mitotic ER partitioning in development and tissue homeostasis.

ER transport in neurons

Neurons are one of the most highly polarized cell types in the body, and the functional and molecular properties of dendrites, the receiving ends of neurons, are necessarily different from those in axons, the transmitting ends. Consistent with this, the organellar composition of axons and dendrites is differentially regulated through highly specific mechanisms. We are currently investigating cytoskeleton-based mechanisms that regulate the transport and functions of the ER in different neuronal compartments. This work is essential to the prevention and treatment of neurodegenerative diseases, many of which are primarily caused by defects in organelle trafficking and homeostasis. This will also facilitate a greater understanding of neuronal response and repair following damage, such as traumatic brain injury (TBI).

Edward Jones, MS

Name: Edward Jones, M.S.

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Instructor

Profile

Mr. Jones has worked for the DoD for his entire adult life, he retired from the US Army and is now an Instructor in the APG department at America's Medical School, USUHS.  Mr. Jones is an Instructor of Anatomy, Neuroscience, and Histology.  He is a dedicated educator who teaches in all preclerkship modules with his biggest contributions in Musculoskeletal, Cardio-Pulmonary-Renal, GastroIntestinal, and Neuroscience modules.

Yumin Zhang, M.D., Ph.D.

yumin zhang

Name: Yumin Zhang, M.D., Ph.D.

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Associate Professor

Email: yumin.zhang@usuhs.edu (link sends e-mail)
Office Phone: (301) 295-9365

Profile

  • Binzhou Medical School, China, M.D., 1985
  • Hebrew University, Israel Ph.D., 1998

The long-term goal of my laboratory is to study the cellular and molecular mechanisms of glial and neuronal toxicity and the pathogenesis of neurodegenerative diseases.

Brain injury is often accompanied with inflammation. Nitric oxide and its reaction product with superoxide, peroxynitrite, are the major toxic species released from the reactive astrocytes and microglia. We are now particularly interested in elucidating the signaling pathways of peroxynitrite toxicity to oligodendrocytes (OLs) using primary cultures from rat and mice brain. Our previous work has suggested that activation of arachidonic acid metabolism plays an important role in the toxicity of peroxynitrite to premyelinating OLs (preOLs) and to mature OLs that produce myelin basic protein. However, distinct cell death pathways are involved in these two cell types. We are now investigating these cell death mechanisms using pharmacological, biochemical and molecular approaches in culture, and testing whether these signaling molecules are critical in the animal models of cerebral palsy and multiple sclerosis, the two major demyelinating diseases found in premature infants and young adults, respectively.

Another area of the research is to study the mechanisms of motor neuron injury in amyotrophic lateral sclerosis (ALS). Although motor neuron dysfunction and degeneration are hallmarks of ALS, recent evidence indicates the toxicity of the mutants of Cu/Zn superoxide dismutase (SOD1), which cause one form of familial ALS, is non-cell autonomous, suggesting that the interplay between neurons and other cell types might play an important role in the pathogenesis of ALS. We will use biochemical, molecular and proteomic approaches to uncover the specific cellular components that contribute to the toxic effects of astrocytes or microglia and the increased vulnerability of motor neurons to the toxic stimuli.

Meera Srivastava, Ph.D.

Name: Meera Srivastava, Ph.D.

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Research Professor

Email: meera.srivastava@usuhs.edu (link sends e-mail)
Office Phone: (301) 295-9365

Profile

  • Indian Institute of Technology, New Delhi, India, 1982

Molecular and genetic approaches to understanding the role of ANX7 in Breast and Prostate Tumorigenesis The ANX7 gene codes for a Ca2+-activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. Evidence for a tumor suppressor function for ANX7 comes from our experiments in which transfection of ANX7 expression caused inhibition of colony forming units. When we overproduced this protein in prostate cancer cells, it reversed their malignant properties and forced them to stop dividing at G2 phase resulting in apoptosis. Introduction of adenovirus containing ANX7 completely eradicated the tumor in nude mice experiments. Total disruption of Anx7 resulted in embryonic lethality in mice, whereas animals heterozygous for Anx7 expression display defects in growth control, Ca2+ signal transduction, endocrine functions and increased incidence of spontaneous tumors. Using a prostate tissue microarray containing 305 patient specimens, we found profound loss of ANX7 protein expression associated with metastases and hormone insensitive local recurrent cancers. In addition, we found that allelic loss of the ANX7 gene occurs on 10q21 in over one third of primary carcinoma of the prostate and breast. In breast carcinomas, ANX7 expression is significantly associated with the presence of metastatic disease and HER2 negative tumors. Currently, we are using genomic, proteomic, yeast two hybrid system to study protein-protein interaction and promoter regulation approaches to identify the ANX7 signaling pathway and its role in cancer in order to develop novel therapeutic tools for prostate and breast cancer.

Nucleolin's role in cell proliferation and cancer

I cloned the human cDNA and gene for the major nucleolar protein called "nucleolin" involved in ribosome biogenesis and localized it to chromosome 2q12-qter. Since Myc directly transactivates the nucleolin gene and nucleolin is the second best androgen regulated gene in prostate cancer, we are focusing our studies in the altered regulation of nucleolin and myc in prostate cancer using molecular and biological approaches.

Molecular basis of vectorial electron transport processes within cells

In early studies on chromaffin granules, which classically secrete catecholamines in response to a calcium pulse, attention was focused on the principal membrane protein cytochrome b561. This cytochrome is responsible for the unique process of vectorial electron transport across the membrane, and transfers electrons from ascorbic acid to dopamine beta hydroxylase (DBH) for the biosynthesis of norepinephrine from dopamine within the vesicle. I cloned the gene for this enzyme and interpreted the sequence in terms of a proposed transmembrane conformation. Cytochrome b561 was differentially expressed in cancer cell lines and was androgen regulated in prostate cancer xenograft model. This new knowledge of the structure of human cytochrome b561 gene, its promoter and its differential expression in cancers provided new insights into the cytochrome b561's role in cancer and is the focus for future research.

Alan Seyfer, M. D.

alan seyfer

Name: Alan Seyfer, M. D.

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Distinguished Professor

Email: alan.seyfer@usuhs.edu (link sends e-mail)
Office Phone: (301) 295-9365

Profile

  • U.S, Military Academy, West Point, 1967; Louisiana State University School of Medicine, 1973

Dr. Seyfer graduated from the US Military Academy at West Point and after serving in the US and Southeast Asia as a platoon leader and battery commander of a missile unit, entered the medical profession. He graduated from the Louisiana State University School of Medicine in New Orleans, completed a general surgery residency at Fitzsimons Army Medical Center (Denver) and then completed plastic surgery training at Walter Reed Army Medical Center (Washington, DC) and a hand surgery/microsurgery fellowship at Duke University (Durham, NC) and Walter Reed. He was assigned to Walter Reed and served as Chief of the Plastic Surgery Training Program as well as Chief of the Hand Surgery Training Program in Orthopedic Surgery before retiring from the US Army and accepting a position in the State of Oregon.

Alan E. Seyfer, surgical photo

As Professor of Surgery and Anatomy at the Oregon Health & Science University School of Medicine, he served as the Division Chief and Program Director of the Plastic/Reconstructive Surgery and Hand/Microsurgery Programs; Co-Director of the Gross Anatomy Course; Chief of Maxillofacial Trauma; and as a Staff General Surgeon in the OHSU Level I Trauma Unit.

His research interests have been in the field of bone morphogenetic proteins and biocompatible bone regeneration materials. His clinical interests have been in the treatment of congenital and acquired disorders of the hand, craniofacial disorders, and chest wall reconstruction.

He has published over 100 articles and chapters and authored a surgical textbook/atlas on chest wall reconstruction. He is certified by the American Board of Surgery and the American Board of Plastic Surgery and received the Certificate of Added Qualifications in Surgery of the Hand. He has served on the Advisory Council for Plastic and Maxillofacial Surgery and the Board of Governors of the American College of Surgeons, and represented the College on the Residency Review Committee for Plastic Surgery. He has also been active in national surgical societies and has served on the editorial boards of national surgical journals.

He serves as the USUHS School of Medicine Course Director of Gross Anatomy, Imaging, and Embryology (Introduction to Structure and Function B & C) and as a surgical consultant at Walter Reed.

Stephen Rothwell

Stephen Rothwell

Name: Stephen Rothwell

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Professor

Links
PubMed Listing

Profile

Education 

Ph.D.  The Johns Hopkins University, Baltimore MD     1986

M.A.S  The Johns Hopkins University, Baltimore MD     1980

Research

My laboratory investigates the proteomics of obesity and appetite control.  Using antibody based assays we are examining the status of appetite regulatory peptides in the plasma of overweight adolescents in collaboration with Pediatric Endocrinologist Dr. Jill Emerick.

Teaching

I am the Module Co-Director for Module 2, Musculoskeletal System of the Pre-Clerkship Curriculum of the F. Edward Hebert School of Medicine, USUHS.  This module covers the basic science and introduction to the clinical aspects of dermatology and the musculoskeletal system.  I also coordinate the physiology and histology content that runs throughout the other modules of the 18 month Pre-clerkship Curriculum.

 

 

Sylvia Poluch

Name: Sylvia Poluch

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Research Assistant Professor

Harvey B. Pollard, M.D., Ph.D.

harvey pollard

Name: Harvey B. Pollard, M.D., Ph.D.

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: Department Chair
Title: Professor & Chair

Affiliated Departments: Molecular & Cell Biology, Neuroscience

Research Interests:
Neuroendocrine and Exocrine Secretory Processes

Email: harvey.pollard@usuhs.edu (link sends e-mail)
Office Phone: (301) 295-9365

Links
Department Website
PubMed Listing

Education

University
M. D. 1973, Ph.D., 1969 University of Chicago

Profile

Profile

Our laboratory focuses attention on the molecular basis of various secretory processes whose dysfunction results in human disease. Neurotransmitter and neurohormone release occur from nerve terminals, endocrine, and exocrine cells by a fusion mechanism sensitive to ionic calcium, GTP, protein kinase C, and other kinases. Two disease-related applications of these interests have been pursued: Synexin (annexin VII, ANX7) is a Ca2+ channel protein and newly identified member of the GTPase Superfamily which uniquely fuses membranes, and is regulated by Ca2+, GTP and various protein kinases. It is also a newly identified component of the "fusion machine" which is believed to mediate docking and fusion during exocytotic secretion. Defects in these processes have been implicated in the pathologies of hypertension and diabetes, among others. These exciting results have prompted Dr. Pollard to investigate how the protein works in vivo using methods of site directed mutagenesis, prokaryotic and eukaryotic mutant protein expression, adenovirus transduction, and transgenic and knockout technologies.

We have also applied our insights from synexin studies to the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which is important for exocrine secretory processes. This protein, which is defective in the most common genetic disease, cystic fibrosis (CF), has nucleotide binding domains which are highly homologous with the annexin gene family. Like annexins, these domains interact specifically with the membrane, and mutations known to cause CF disrupt these interactions. Molecular analysis of the structure of these domains have led to our development of compounds which are currently being tested clinically for treatment of cystic fibrosis. In addition to conventional molecular methods employed for this study, our other approaches include fluorescence spectroscopy, confocal microscopy, lipid biochemistry, and organic synthesis.

John T. O'Neill, Ph.D.

Name: John T. O'Neill, Ph.D.

Department of Primary Appointment: Anatomy, Physiology & Genetics
Position: USU Faculty
Title: Research Assistant Professor

Email: john.oneill@usuhs.edu (link sends e-mail)
Office Phone: (301) 295-9365

Profile

Johns Hopkins University, 1980

Research Interests:

As an important organ system of the body, the brain has evolved processes that ensure it receives an adequate supply of oxygen and nutrients. Under stressful conditions (shock, anoxia, asphyxia), as well as changes in blood pressure, the brain blood supply remains stable, and blood flow is altered to accommodate changing needs for oxygen and glucose. Dr. O'Neill is investigating these adaptive processes by determining how some molecules (nitric oxide, adenosine, hemoglobin and neurotransmitters) act to control blood flow in the brain and the eye. Several approaches to measure blood flow are employed including, radioactive and colored microspheres, electromagnetic flow probes, and laser-Doppler techniques.

He is particularly interested in developmental aspects of blood flow control. Newborns can sustain severe brain damage when the blood, oxygen or nutrient supply to the brain is inappropriate. It appears that some of the control mechanisms operative in the adult are not present or are not fully developed in the newborn. Alternatively, some distinct mechanisms are operative during the newborn period, but are not present in adults.

Dr. O'Neill is currently exploring the interrelationship of prostaglandins and nitric oxide in the control of brain blood flow during hypotension and hypertension. He is also examining the expression of an early immediate gene (Egr-1) and its protein product during cerebral hypoxia and resuscitation. This gene is suspected to initiate many of injurious responses to ischemia and reperfusion.

Pages

Subscribe to RSS - Anatomy, Physiology & Genetics