The Department of Laboratory Medicine and Pathology at the University of Minnesota Medical School is committed to bringing leading-edge basic and applied research and innovation to patient care.
The research-intensive faculty within the department have several major focus areas including cancer, immunology, cardiovascular disease, renal disease, diabetes, and genetics. The faculty consist of tenured associate and full professors, several of which currently hold endowed chairs or professorships. They interface with University of Minnesota departments and centers such as the Center for Immunology, Masonic Cancer Center, and the Institute for Translational Neuroscience.
Downtown Minneapolis viewed from a basic research laboratory
Brenner tumor (IHC for E-cadherin)
Polychromatic crystalline keratopathy of the cornea
Pap smear with endocervical adenocarcinoma in situ
Macrophages (in red) surrounding a growing ductal structure in the mammary gland
Human melanoma cells in culture
A human melanoma cell. The arrows point to cell-surface receptors used for metastasis. These receptors are targets for drug therapy.
Bone marrow touch imprint, Wright-Giemsa stained, from a patient with smoldering plasma cell myeloma
Mouse brain neurons (red) and associated tau neurofibrillary tangles (green). Tau tangles are implicated in Alzheimer's disease.
Hogquist named LMP vice chair for research
Kris Hogquist has been named Laboratory Medicine and Pathology Vice Chair for Research. In this new role, Kris will serve as chair of the Research Advisory Committee (RAC), provide an avenue for peer review of grant applications, identify strategic initiatives to expand on the department’s existing research accomplishments and help support the chair’s research vision for the department.
Kris holds the David M. Brown Endowed Professorship and is Associate Director of the Center for Immunology. In 2015, she was inducted into the AHC Academies for Excellence in Health Research. Her citation reads: "Kristin Hogquist is widely recognized by the international scientific community for her many important contributions in the field of immunology. Her work helped to put the University of Minnesota on the map as a major international center for immunology research.”
Kris was honored with the Dean's Distinguished Research Lectureship (DDRL) in 2016. Her lecture was entitled "Why do we need a thymus?"
Kris received the American Association of Immunologists (AAI) Distinguished Service Award in 2014 for her outstanding service to the immunology community as Chair of the AAI Program Committee, 2009–2012.
Kris's research program is focused on T cell development in the thymus, particularly positive and negative selection, tolerance, and T cell selection in immune homeostasis and response. Her group identified the first naturally occurring self-peptides involved in the positive selection of T cells, and studied their affinities for the T-cell receptor when bound to MHC, providing evidence for an affinity model of thymic selection. She has published more than 140 research and review papers and three book chapters. Her paper T cell receptor antagonist peptides induce positive selection, published in Cell in 1994, was selected as a “Pillars of Immunology” article by the Journal of Immunology.
Kris received a bachelor's degree from the College of St. Catherine in St. Paul. She earned her doctoral degree in Immunology from Washington University in St. Louis and did post-doctoral work at the University of Washington, where she first became interested in T cell development. She started as an Assistant Professor in our department in 1995. She has trained over 25 graduate students and post-doctoral fellows and maintains a strong interest in mentoring the next generation of scientists.
Core pathology EPAs proposed for basic science courses
At the Association of Pathology Chairs (APC) meeting in San Diego last month, Sarah Williams spoke about how the core Entrustable Professional Activities (EPAs), developed by the AAMC, could be used as a framework for medical competencies or outcomes during the preclinical years of medical school.
Medical knowledge essential for many of the core EPAs is acquired during the basic science courses in medical school. Williams, with help from Debbie Powell, presented a poster entitled “Core EPAs in Basic Science Courses: An Important Role for Pathology.” The LMP team has developed an online system for providing feedback to medical students during the second year pathology course for two of the core EPAs: EPA 2 (develop a prioritized differential diagnosis and select a working diagnosis) and EPA 3 (recommend and interpret common diagnostic and screening tests). The selected EPAs reinforce that pathologists add value and can directly play a role in preparing students for clinical experience.
The online system developed by the LMP team charts levels of achievement and also allows students to do self-evaluations to compare to the faculty evaluations. In an initial pilot study, students were eager to understand how case-based pathology teaching sessions allowed them to become better prepared for their clinical rotations and to realize the value of informed selection of laboratory tests.
The results support the feasibility and utility of an online platform for assessment and narrative feedback in evaluating two of the core EPAs in a basic science course during the pre-clinical years of medical school. The online platform also fulfills the LCME’s guidelines for formative assessment and feedback.
Li targets plasma lipids and proteins as potential biomarkers for Alzheimer’s disease
Alzheimer’s disease (AD) is a research and public health priority worldwide. In the United States alone, there are an estimated five million people with AD. The annual cost of treating them is more than $230 billion, a figure projected to increase to more than $500 billion by 2040 unless effective therapies are developed to prevent, slow or arrest this devastating disease. Drug trials over two decades targeting amyloid plaques, long thought to be key proteins in AD pathobiology and progression, have failed.
LMP assistant professor Danni Li and her research colleagues are taking a different approach, focusing instead on plasma lipoproteins and metabolites that could serve as biomarkers for dementias and age-related cognitive and physical function decline. Li is also exploring how exercise and fatty acids may work together to improve cognition.
The NIH’s National Institute on Aging (NIA) has awarded Li a four-year $2 million R01 grant to study “Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and/or cognitive training in amnestic mild cognitive impairment.” NIA has also awarded her a two-year $253,000 R21 grant to identify specific plasma lipids as biomarkers of demyelination and neurodegeneration responsible for physical function decline in older adults.
"I have been very lucky and grateful to work with mentors and collaborators who have provided me with invaluable feedback," Li said.
A key resource for Li’s metabolomics and proteomic studies is NIH’s Atherosclerosis Risk in Communities (ARIC) study. ARDL’s involvement in the study enabled her to established important collaborations, particularly with LMP professor emeritus John Eckfeldt. Preliminary analysis of plasma lipids from the ARIC study revealed that lower levels of specific lipids, which may be involved nerve cell demyelination and degeneration, are associated with comparatively poor physical function. The specific aims of Li and her fellow investigators are to determine the association of the target lipid with physical function in older adults.
For her research on blood biomarkers, aerobic exercise, cognitive training and improving cognition, Li will build on the ACT Trial, a study directed by School of Nursing professor Fang Yu. In the ACT Trial, aerobic exercise and cognitive training are combined in subjects with amnesic mild cognitive impairment, which often precedes AD. Li and colleagues have found preliminary evidence that certain plasma lipids have unique mechanistic associations with cerebral amyloidosis and neurodegeneration, both characteristic of AD.
Li’s hypothesis is that these protein levels change in response to aerobic exercise and cognitive training, which would potentially make them predictive biomarkers, paving the way for early therapeutic interventions.