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.
Linden joins Steering Committee for MDS-AML education program
Mike Linden recently joined the Steering Committee for MDS+AML MATTER, a free education program focused on myelodysplastic syndrome and acute myeloid leukemia that offers continuing education credit. It is hosted in partnership by the American Society of Hematology, American Society for Clinical Pathology, National Marrow Donor Program, Oncology Nursing Society, and The France Foundation.
In conjunction with hematopathologists, hematologists, cytogeneticists, and oncologic nurses, Mike will design course curriculum and will be presenting four sessions this fall at the 2018 ASCP Annual Meeting (Baltimore, MD), MDS+AML Matter Summit (Pittsburg, PA), the 2018 ASH Annual Meeting (San Diego, CA), and the 2019 Highlights of ASH (San Francisco, CA).
Here's a link to the Pittsburgh meeting.
Regents approve fellowship program
The Board of Regents recently approved the Medical School's application for a new Gastrointestinal (GI) Pathology Fellowship program. One fellow will be accepted per year and will rotate in the East and West Bank laboratories. Trainees who have finished their AP or AP/CP training are invited to apply.
LMP’s Division of Anatomic Pathology receives more than 7000 luminal gastrointestinal (GI) and pancreato-biliary, 600 liver and 700 GI consult cases annually, making the GI pathology service the home of the heaviest volume of cases among all surgical pathology subspecialties. The surgical pathology workup in this field integrates very well with LMP’s Molecular Pathology and Genomics division (for familiar cancer and prognostic markers testing) and cytopathology (for fine needle aspiration biopsy diagnosis of pancreatic lesions). AP’s practice focuses on three main areas of GI Pathology: oncologic pathology, transplant medicine, and the multidisciplinary management of inflammatory bowel disease.
Contact GI Pathology Fellowship program director Mahmoud Khalifa for more information.
Jameson homes in on T cell self-tolerance
As a pioneer in transplant surgery, the University has been at the forefront of immunology for more than half a century, exploring how the risk of transplant rejection by the human immune system can be minimized. Steve Jameson and his colleagues in the Center for Immunology aim to keep immunological research at the forefront for making advances in enhancing vaccines and in treating autoimmune disease and cancer.
Jameson’s lab has been testing how vaccines work in the T cell context. In experimental studies in mice, he and his colleagues have applied vaccines to skin to see whether epicutaneous application was sufficient to generate an effective memory CD8+ T cell response that would be protective against bacterial and viral infections. That work has opened up a new research avenue. Jameson was recently awarded a five-year, $2.4 million National Institute of Allergy and Infectious Diseases grant for his project “Making and breaking of CD8+ T-cell self-tolerance.”
In cancer immunotherapy, one goal is to provoke an immune response that targets cancerous cells but leaves normal healthy cells of the body alone. In many cases, however, cancer cells evade destruction by only expressing targets for the immune system that are shared on healthy cells. This means that, in those cases, effective cancer immunotherapy would likely lead to damage to normal cells – such as destruction of the pigmented skin cells called melanocytes as the price to pay for controlling melanoma. Autoreactive CD8+ T cells are typically thought to be eliminated (a process called “clonal deletion”) during immune system development in order to prevent an auto-immune reaction against healthy tissues. Over the past two decades, however, immunologists have found that “self-tolerance” can render CD8+ T cells to be physically present but in a “non-responsive” state called anergy. Understanding the mechanistic basis for anergy – and ways in which this form of self-tolerance can be “broken” for tumor immunotherapy – is the focus of the new work by Jameson and his fellow investigators.
“Our data show that mouse T cell tolerance to proteins on normal melanocytes typically involves a form of anergy, not deletion,” Jameson said. “In the proposed studies we will investigate the basis for this form of tolerance.” He said his studies could have broad significance for understanding autoimmune diseases such vitiligo, psoriasis, alopecia and other skin conditions that can all be caused by T cell autoimmune responses to melanocytes. They also may be clinically relevant by revealing potential mechanisms of CD8+ T cell self-tolerance disruption. Immunotherapy with immune checkpoint inhibitors, which has revolutionized the treatment of melanoma, is a case in point.
Jameson will employ a threefold approach in his investigations of CD8+ T cell self-tolerance:
- Explore the basis of CD8+ T cell anergy.
- Test the reversibility of anergy.
- Examine how the lack of physiological exposure to normal skin infections and inflammation may compromise the value of current mouse models.
Jameson and his research team will use acute skin inflammation and infection models in their studies. Team members will also use inbred mice that have been naturally infected with normal mouse microbes, so-called “dirty” mice. Jameson helped to develop the model, which more closely mimics the human immune system experience than do standard laboratory mice models.