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.
Kelsey McIntyre, PhD, joins LMP
Kelsey McIntyre, Ph.D. will join our Cytogenetics / Molecular Diagnostics faculty effective July 31. She comes to the University from Harvard Medical School where she was a Clinical Cytogenetics Fellow (2017) and a Clinical Molecular Genetics Fellow (2018).
McIntyre earned a B.S. degree in natural sciences and a PhD. degree in genetics from the University of Wisconsin-Madison. She began her research career as an undergraduate, combining genetics and microscopy to interrogate early cell divisions in the C. elegans embryo and mitochondrial activity in mouse embryonic stem cell-derived cardiomyocytes.
For her graduate studies, McIntyre joined the laboratory of Xin Sun to study the molecular mechanisms of organogenesis. As an American Heart Association Predoctoral Fellow, McIntrye identified a role for Slit-Robo signaling in foregut morphogenesis in a mouse model of congenital diaphragmatic hernia. Further studies led to her discovery that Robo genes are also involved in pulmonary neuroendocrine cell development and function as airway sensors.
McIntyre's three-dimensional imaging study of lung development uncovered new insights into the key cellular events that occur during alveologenesis. That paper, A three-dimensional study of alveologenesis in mouse lung," earned her the 2016 Society for Developmental Biology's outstanding paper award.
During her Harvard fellowships in clinical cytogenetics and clinical molecular genetics, McIntyre interpreted results and wrote reports for each clinical service in the cytogenetics laboratory including karyotype, FISH and microarray in constitutional (prenatal, pediatric, adult) and oncology (solid tumors and hematologic malignancies) settings. She also evaluated variants, wrote reports for >400 gene NGS panel for cancer testing, and analyzed non-NGS cancer molecular assays. As a consultant to Claritas Genomics, she analyzed and interpreted clinical exomes.
McIntyre led the validation and launch of the Affymetrix OncoScan array for cytogenomic analysis of FFPE tumors and products of conception at Brigham and Women's Hospital and Harvard Medical School. In that capacity she collaborated with physicians in neuropathology, renal pathology, cytology, thoracic surgery, and OB-GYN to determine clinical utility for array testing.
Regents approve fellowship program
Pennell/Blazar study achieves milestone
New immunotherapies — therapies that enlist and strengthen the power of a patient’s immune system to attack tumors — are revolutionizing the treatment of cancer. One of the leading opportunities is chimeric antigen receptor (CAR) T cell therapy. T cells are removed from the patient and genetically engineered to produce special receptors that allow them to recognize and attach to a specific protein, or antigen, on tumor cells. Last year, the FDA approved two CAR T-cell therapies, one for the treatment of children with acute lymphoblastic leukemia and the other for adults with advanced lymphomas.
But CAR T therapy is not without risks. Some patients experience life-threatening complications. LMP immunologist Chris Pennell together with Regent’s professor of pediatric blood and marrow transplantation Bruce Blazar and the immunotherapy group at the Masonic Cancer Center have developed a mouse model that replicates the anti-tumor efficacy and toxicities experienced by patients treated with CD19 antigen-specific CAR T-cells. Pennell is lead author of “Human CD19-Targeted Mouse T Cells Induce B Cell Aplasia and Toxicity in Human CD19 Transgenic Mice” published in Molecular Therapy. In a commentary accompanying the article, CAR T-cell therapy pioneer Carl June and his University of Pennsylvania colleague Marco Ruella called the report “a milestone in the development of preclinical models able to predict human CAR T toxicity and efficacy.”
CAR T-cell therapy has had the best success so far in treating patients with B cell malignancies, Pennell said. “One reason is that the B cells express a relatively unique antigen, CD19, that can be targeted by CAR T-cells. This permits tumor killing via ‘on-target on-tumor’ recognition by CAR T-cells. Unfortunately, the major limitations of the approach are ‘on-target off-tumor’ toxicities due to CD19 expression on healthy B cells.”
The toxicities include sometimes fatal systemic inflammation and central nervous system toxicities, the underlying causes of which are not well understood, Pennell said. “Because the mice we use express human CD19 on both healthy and malignant B cells, we can study ways to eliminate tumors while simultaneously limiting toxicities,” he said. “We can use the power of mouse genetics to understand the mechanisms that underlie these toxicities using clinically-relevant CAR constructs.” The long-term goal of Pennell and his colleagues is to develop strategies that maintain CAR T efficacy but minimize toxicity.
By developing predictive tools that can identify strategies with minimal toxicities, Pennell, Blazar and their fellow investigators are helping to secure CAR T-cell immunotherapy’s designation as the American Society of Clinical Oncology’s “2018 advance of the year.”