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Research

The Department of Laboratory Medicine and Pathology has both strong basic and clinical research components. It is unique in this respect in comparison to many other clinical departments of the medical school, and has a seat at both the Clinical Departments Heads and Basic Science Council meetings of the Dean’s office.


Contents


Research Funding

The Department of Laboratory Medicine and Pathology has consistently been among the top medical school pathology departments in the United States in NIH Grant funding in recent years, ranking 18th in 2010 according to the BRIMR Funding Rankings.


Basic Research

The Research Advisory Committee (Drs. LeBien, McCarthy, Mescher and Orr) serves as the primary advisory group to the Department Head with respect to basic research matters. The major areas of research emphasis in the department include cancer, immunology, and human genetics. The department has been very effective in promoting these efforts by working in partnership with the Comprehensive Cancer Center, and the Center for Immunology. Much of the leadership of these Medical School-wide centers and institutes and their programs is provided by members of the department faculty. Through these partnerships the department has strengthened its own research base while making major contributions to the research enterprise of the institution as a whole. We are fundamentally committed to this matrix type of situation in the future. This posture provides tremendous opportunities for the department.

Cancer Biology

The department has a very close working relationship with the University of Minnesota's Masonic Cancer Center, an NCI-designated Comprehensive Cancer Center since its inception. This is reflected by research strength, collaborative successes in establishment and maintenance of shared resources, and collaborative successes in the recruitment of new faculty. Many of the department’s faculty play major leadership roles in the Cancer Center. Tucker LeBien is Associate Director of the Cancer Center for Basic Sciences and Director of the Flow Cytometry Shared Resource. Steve Hecht is the Carcinogenesis & Chemoprevention Program leader and Director of the Analytical Biochemistry Shared Resource. James McCarthy is the Tumor Biology & Progression Program leader. Yoji Shimizu is the Tumor Immunology Program leader. Betsy Hirsch is Director of the Cytogenetics Shared Resource. Amy Skubitz and Stephen Schmechel are co-Directors of the Tissue Procurement Facility Shared Resource.

The research interests of the department’s cancer biology faculty include:

  • Khalil Ahmed, Ph.D., is studying the functional role of protein kinase CK2 in cancer cells, employing prostate cancer and head-and-neck cancer as experimental models.
  • Scott Dehm, Ph.D., focuses on the role of the androgen receptor (AR) in prostate cancer development and progression.
  • Myron Gross, Ph.D., develops biomarkers and applies them in epidemiologic studies for the identification of risk factors and mechanisms associated with cancer and other chronic diseases.
  • Steve Hecht, Ph.D., studies mechanisms and prevention of tobacco-induced cancer, focusing on tobacco carcinogens, their metabolism and DNA adducts.
  • James McCarthy, Ph.D., studies the importance of changes in microenvironment in the growth, invasion and progression of prostate tumors and melanoma.
  • Kaylee Schwertfeger, Ph.D., focuses on the correlation of inflammation within the tumor microenvironment with increased invasiveness and poor prognosis in many types of cancer, including breast cancer.
  • Amy Skubitz, Ph.D., is examining basic mechanisms associated in ovarian cancer spread, and the interactions of beta-1 integrin subunits and CD44 on the surfaces of ovarian carcinoma cells and mesothelial cells.
  • Michael Wilson, Ph.D., is studying the development/function of the prostate gland and evaluating mechanisms associated with pathology of the prostate gland.

Immunology

The department has a long history of strength in immunology research, and faculty of the department spearheaded the efforts that led in 1995 to the establishment of the Medical School-wide Center for Immunology. The Center was initiated in the department. The Center has over fifty members from across the Medical School and School of Veterinary Medicine, including twelve faculty whose research programs are housed in Center space. Of this multi-departmental group, five of the twelve are members of Laboratory Medicine and Pathology including Matthew Mescher, the director of the Center. A departmental search is currently underway that will add another investigator to the group. Several additional departmental faculty with research interests in immunology are housed in the Cancer Center.

The immunology faculty members have a very strong record of sustained external funding, which provides a large fraction of their salaries, and their scholarly productivity is outstanding as measured by publications and citations. They are also a highly interactive group, with numerous collaborations with other investigators within the department, and in other departments and institutions. In addition, while their primary focus in most cases is on basic immune mechanisms and the studies employ murine models, many also have active collaborations involving human immunology and translational efforts. As examples, Dr. Hogquist has recently begun a collaboration with Dr. Balfour to study the role of T cells in the development of immuno-pathologic disease after primary exposure to Epstein Barr Virus, and Dr. Mescher has an ongoing collaboration with Cancer Center investigators testing a novel immunotherapeutic approach for targeting CD8 T cells in melanoma and breast cancer trials.

The research interests of the department’s immunology faculty include:

  • Michael Farrar, Ph.D., is studying how cytokines and cytokine dependent signal transduction pathways regulate lymphocyte development.
  • Stephen Jameson, Ph.D., is studying the mechanisms that regulate the development and maintenance of T cells in the body.
  • Tucker LeBien, Ph.D., is characterizing the collective marrow microenvironmental stimuli that regulate the developmental fate of normal and leukemic human B cell precursors.
  • Matthew Mescher, Ph.D., is elucidating the basic mechanisms involved in CD8 activation and tolerance induction, and applying these findings to murine models of tumor immunotherapy.
  • Christopher Pennell, Ph.D., is studying the role of stress proteins in the modulation of immune responses in order to optimize their use in cancer therapy.
  • Yoji Shimizu, Ph.D., is investigating the intracellular signal transduction events that regulate adhesive interactions critical for effective antigen-specific immune responses.

Human Genetics

The human genetics group within the department utilizes a variety of genetic and molecular approaches to examine mechanisms of disease. Two particular areas of strength are the genetics of cancer and neurodegenerative disorders. In many instances partnering with the Institute of Human Genetics has provided research space to faculty.

  • Mike Koob, Ph.D., uses genetic approaches to study mitochondrial disorders and the neurodegenerative disease spinocerebellar ataxia type 8.
  • Harry T. Orr, Ph.D., uses genetic, behavioral and cell biological approaches to explore the pathogenesis of polyglutamine neurodegenerative diseases.

In addition to the above, Drs. Myron Gross, Betsy Hirsch, and Michael Tsai study human genetics -- they are listed in the Clinical Research section below.

Additional Research Areas

  • Lynda Ellis, Ph.D., focuses on developing bioinformatics tools that support life sciences research, including development of an innovative microbial biotechnology database.
  • Stanley Finkelstein, Ph.D., is designing and evaluating home telehealth systems and studying their application to monitoring of lung transplant recipients and in chronic disease management.
  • William Gleason, Ph.D., is investigating the design, synthesis and applications of polymeric biomaterials, and the modeling of biological systems of clinical importance.
  • Gundu H. Rao, M.D., has research interests in the areas of heart disease, atherosclerosis and thrombosis.
  • Stuart Speedie, Ph.D., is studying the impacts of health information technologies, including telehealth and home telehealth, and the application of informations systems in clinical research.
  • Carol Wells, Ph.D., is investigating interactions of microbes with intestinal epithelial cells, and the mechanisms that allow the microorganisms to enter tissues, leading to systemic infections.
  • James White, M.D., is studying the biology of platelets and the structural and functional abnormalities of platelets that contribute to disease.

Clinical Research

Advanced Research and Diagnostic Laboratory

Dedicated to serving research studies that are from moderate to very large in size and mostly funded by NIH. This section was originally developed by Michael Steffes, M.D., Ph.D., when our clinical laboratories were designated as the central lab for the Diabetes Control and Complications Trial (DCCT) in the late 1980s. It has grown from a few technologists and technicians then to now having over 25 FTE assigned to research study testing. It has served as the central lab for some of NIH’s largest studies (e.g., ALLHAT, a clinical trial of antihypertensive agents with ~40,000 participants; HEIRS, one of NIH’s largest ever genetic screening studies that looked for iron overload disorders in over 100,000 participants; MESA, a multi-ethnic study of preclinical cardiovascular disease with about 16,000 participants; etc.)

Clinical Chemistry

  • John Eckfeldt, M.D., Ph.D., has served as PI for the central laboratory in many very large epidemiologic observational studies and clinical trials of cardiovascular disease and iron absorption and storage disorders.
  • Myron Gross, Ph.D., develops biomarkers and applies them in epidemiologic studies for the identification of risk factors and mechanisms associated with cancer and other chronic diseases.
  • Michael Steffes, M.D., Ph.D., has served as PI for the central laboratory in many large epidemiologic observational studies and clinical trials of diabetes, renal disease, and cardiovascular disease.
  • Michael Tsai, Ph.D., has served as PI for the central laboratory in many large epidemiologic observational studies and clinical trials of cardiovascular disease, lipid disorders, homocysteine disorders, diabetes, and also play important roles in large-scale candidate gene and genome-wide association studies such as CARe and SHARe.
  • Anthony Killeen, M.D., Ph.D., is involved with assessment of clinical laboratory performance and has a specific interest is in the development of accuracy based proficiency testing. He is co-investigator on several external grants for performance of clinical laboratory testing for multi-center studies.

Molecular and Cytogenetics

  • Betsy Hirsch, Ph.D. serves as a reviewer of cytogenetics for a number of the cooperative cancer groups, as Director the cytogenetics core facility for the cancer center, and investigates chromosome instability disorders and genotoxic damage by molecular cytogenetic techniques.
  • Michelle Dolan, M.D., is trained in anatomic as well as clinical pathology, and has research interests related to bridging these two areas, concentrating especially on FISH as applied to solid tumors, both touch imprints, and paraffin-embedded tissues.

Hematopathology

  • Robert McKenna, M.D., focuses on characterization of clinical and biologic subsets of lymphoid neoplasms and clonal myeloid disorders through applied immunophenotypic and genetic/molecular techniques

Immunology/Histocompatibility Testing

  • David Maurer, Ph.D., has an interest in methods for the laboratory measurement of graft-specific anti-HLA antibodies for clinical patient management and for improving transplant outcomes.

Transfusion Medicine and Cellular Therapy

  • Jeffrey McCullough, M.D., has conducted transfusion related research for more than 30 years with funding from multiple sources including currently the NIH. Currently active research includes novel cellular therapies, clinical trials of platelet or granulcyte transfusion, and trials of pathogen inactivated blood products.
  • David McKenna, M.D., is involved in a variety of activities related to advancing the field of cellular therapy, including his role as co-investigator both in the Production Assistance for Cellular Therapies (PACT, an NHLBI initiative) and in the Cardiovascular Cell Therapy Research Newtork (CCTRN of NHLBI).
  • Claudia Cohn, M.D., Ph.D.
  • Shanna Morgan, M.D.
  • Nicole Zantek, M.D.

Infectious Diseases

  • Patricia Ferrieri, M.D., has a very active research program investigating the basic and clinical aspects of bacterial disease, especially Group B streptococci and pneumococci.
  • Henry Balfour, M.D., has a very active research program investigating the basic and clinical aspects of a variety of viral diseases, including HIV, CMV, and EBV.
  • Sophie Arbefeville, M.D.

Research in Anatomical Pathology (AP)

A research laboratory was created in the early 1970s to support academic endeavors in the division of anatomical pathology. For many years the laboratory provided almost exclusively immunohistochemical stains with some in-situ DNA hybridization for EBV. Several hundred publications from AP faculty members were produced with the support of this laboratory in the first 25 years of its existence. In the past 10 years this laboratory has expanded its capabilities to include automated immunohistochemistry and in-situ hybridization, tissue microarrays and laser capture microdissection in support of research in the division.

The explosive development of biomedical knowledge at molecular and genetic levels has had a strong impact on the present and future focus of this research laboratory. Presently there is ongoing and planned future implementation of additional techniques in this laboratory that take advantage of advances in molecular biology combined with a morphologic approach. These techniques include among others fluorescent in-situ hybridization, in-situ DNA and RNA hybridization, in-situ RT-PCR, laser capture microdissection, micro-array technology for genomics and proteomics, and other nucleic acid-based techniques. This laboratory will be incorporated into the BioNet, Biological Specimens Repository and Research Services center that supports research for department faculty members and for researchers in other departments, centers and institutes. In addition to the above, it will provide cell cultures, banked tissue and cells, and material for genomic and proteomic studies.

The Section of Neuropathology has a separate research laboratory, from which Dr. Clark collaborates with basic researchers in cerebellar degenerative diseases and Dr. SantaCruz collaborates with other researchers in the neuropathology of dementia.

Faculty Expertise and Research Focus


Faculty members in Anatomic Pathology carry out research projects in their areas of expertise. Many of these projects are primarily pathology-based; others are done in collaboration with basic researchers and clinical colleagues. An analysis of the Annual Faculty Member Reviews in the Division of Anatomic Pathology indicates that the estimated time allocation for research ranges from 5% to 50%.

  • Dr. Clark studies inherited neurodegenerative diseases, with particular focus on dominantly inherited diseases such as the spinocerebellar ataxias and myotonic dystrophy.
  • Dr. Jon Ritter
  • Dr. Hannah Krigman
  • Dr. Robyn Reed

 


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