LCOM & Department News

Seward Lab Lands Two-Year National Cancer Institute R21 Grant

April 18, 2023 by Katelyn Queen

UVM Cancer Center member David J. Seward, M.D., Ph.D., assistant professor of pathology and laboratory medicine, received a prestigious two-year National Cancer Institute R21 grant to investigate why lung cancers with a certain set of mutations demonstrate immunotherapy resistance.

David Seward, M.D., Ph.D., Associate Member, UVM Cancer Center

Grant will fund research on immunotherapy resistance in lung cancer

In the US, lung cancer is the leading cause of cancer-related deaths. Many advances in science have led to new and improved therapeutics, including options such as immunotherapy. Immunotherapy works to improve outcomes by promoting a patient’s immune system to find and remove cancer cells in the body. 

One specific immunotherapy used in lung cancer is check-point inhibitor therapy targeting the PD-L1/PD1 interaction. PD1 is a receptor on T-cells of the immune system and is known to play a role in tumor immune evasion. With check-point inhibitor therapy, anti-PD1 monoclonal antibodies target PD1 to prevent tumor immune evasion and promote cancer cell death. While some patients respond quite efficiently to immunotherapy, a subset has little to no response. Importantly, this “non-responder” group has been characterized as having a specific set of genetic mutations, one example being oncogenic KRAS variants in combination with STK11 loss of function. Why this combination of mutations results in immunotherapy resistance remains unknown.

UVM Cancer Center member David J. Seward, M.D., Ph.D., assistant professor of pathology and laboratory medicine, received a prestigious two-year National Cancer Institute R21 grant to investigate why lung cancers with this set of mutations demonstrate immunotherapy resistance. Funded by the National Institute of Health, the team seeks to discover why certain patients exhibit resistance to anti-PD1 therapy and identify mechanisms that overcome this resistance to promote response to immunotherapy. 

Working in collaboration with the labs of UVM Cancer Center members Paula Deming, Ph.D., associate professor of biomedical and health sciences, Jonathan Boyson, Ph.D., associate professor of surgery, and Ralph Budd, M.D., university distinguished professor of medicine and microbiology, the Seward Lab will use mouse models to better understand why STK11 loss of function correlates with anti-PD1 therapy resistance in patients with KRAS-driven lung cancers. The scientists hypothesize that loss of STK11 allows the tumor to fool the immune system causing the wrong immune cells to be called into action. In theory, this immune system confusion could lead to an absence of the cells targeted by anti-PD1 therapy. Once the lab has identified potential mechanisms by which STK11 mutations disrupt immune system activation they plan to test various drug interventions that would work to restore anti-PD1 therapy effectiveness in patients who suffer STK11 mutations. 

For more information about this project and others follow @SewardLab on Twitter. 

 

Past Department Highlights

Mark_FungCongratulations to Dr. Mark Fung, M.D., PhD., Professor Pathology and Laboratory Medicine, on receiving the 2023 College of American Pathologists (CAP) Lifetime Achievement Award. Dr. Fung is a nationally recognized expert in transfusion medicine. (10/2023) 

Congratulations to Jessica Crothers, M.D., Assistant Professor Pathology and Laboratory Medicine, on achieving the Notice of Special Interest Team Science award from NIAID for: "Effects of the gut microbiota on oral vaccine response in adults and children." (10/2023)

Nicole BouffardCongratulations to Nicole Bouffard on being awarded the "Scientific Research Staff Award" for 2023. This was presented to Nicole at the September 21, 2023, LCOM Research Excellence Award Ceremony. This is a great honor for Nicole and the Department of Pathology and recognizes her contributions and importance to the department and MIC. (10/2023)

Congratulations to Brian Cunniff, Ph.D., Assistant Professor Pathology and Laboratory Medicine, on being awarded a $1.6 million R01 grant by the National Institute of General Medical Sciences to study the role of mitochondrial trafficking in regulating cell migration, a key feature of metastatic tumors. (9/2023)

Congratulations to Yvonne Janssen-Heininger, Ph.D., Professor Pathology and Laboratory Medicine, on becoming a University of Vermont Cancer Center Program Co-Leader, Cancer Cell. (9/2023)

Congratulations to the following pathology members on receiving research support funds in April 2023. Recipients were: John Kennedy, M.D., $6520 for morphologic and immunohistochemical re-evaluation of renal cell carcinomas exhibiting papillary architecture, with emphasis on tumors demonstrating "type 2" morphology. Yvonne Janssen-Heininger, Ph.D., $15,000 for a joint initiative between RBP, UVM Cancer Center, and faculty in the Department of Chemistry. Megan Tarte $745 for Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Disease Conference. Albert van der Vliet, Ph.D., $14,400 for Redox processes in macrophage activation in IPF. (9/2023)

Congratulations to the following faculty members on their promotions: Vikas Anathy, Ph.D., to Professor with tenure, Bronwyn Bryant, M.D., to Associate Professor, John DeWitt, M.D., Ph.D., to Associate Professor, Sarah Nowak Ph.D., to Associate Professor, and Christi Wojewoda, M.D., to Professor. (6/2023)

Bei Zhang, M.D., M.S., Ph.D., MLS(ASCP), associate professor of pathology and laboratory medicine, did an educational scholarship session titled "Activate Students Learning Outside Classroom." at the 8th International meeting of the Association of Biochemistry Educators. Dr. Zhang also conducted two additional workshops with other ABE members titled "Linking Clinical Presentations to Their Biochemistry: A novel ABE Clinical-Biochemistry Curricular Treat Mapping Educational Tool.", and "Getting to Clerkship and Beyond: Crafting Biochemistry Learning Objectives that Connect and Integrate Basic Science Concepts with Clinical Application." (5/2023)

Congratulations to Dr. Maureen Harmon, M.D., associate professor of pathology and laboratory medicine, and Dr. Amer Abu Alfa, M.D., assistant professor of pathology and laboratory medicine for being recognized by medical students for their professionalism. Dr. Harmon was recognized for social responsibility and Dr. Abu Alfa was recognized for compassion. (5/2023)

Congratulations to Mary Cushman, Ph.D., M.Sc., professor of medicine and pathology and laboratory medicine, on being named a University Distinguished Professor of Medicine, Hematology/Oncology Division, and Pathology and Laboratory Medicine. (5/2023)

View the story Mammograms of a study by Sarah Nowak, Ph.D., assistant professor of pathology and laboratory medicine, and researchers at the UVM Cancer Center showing data that fewer women being screened for breast cancer. (4/2023)

vandervliet-habibovic420x280A new study by Albert van der Vliet, Ph.D., professor of pathology and laboratory medicine, and a team of University of Vermont (UVM) researchers is honing in on why people with asthma often have worse symptoms if they are obese. This new research demonstrates that the gene DUOX1 likely contributes to the connection between obesity and asthma.  The research was published ahead of print in the American Journal of Physiology-Lung Cellular and Molecular Physiology and was highlighted as an APSselect article for March 2023. Albert van der Vliet, Ph.D., was the senior author on the paper, along with department of pathology and laboratory medicine coauthors Aida Habibovic, lab research technician;Litiele Cruz, Ph.D., visiting scholar; Vikas Anathy, Ph.D., associate professor; University Distinguished Professor Yvonne Janssen-Heininger, Ph.D.; and additional team members and authors from UVM. Read the full LCOM News story LCOM News (4/2023)

Congratulations to Bronwyn Bryant, M.D., Assistant Professor of Pathology and Laboratory Medicine, for having your proposal, Consequential Validity of Entrustable Professional Activities in Pathology Residency Training selected to receive a Frymoyer Scholars Program project of $48,000 to be funded July 1, 2023 through June 30, 2025. (4/2023)

Congratulations to Martin Chang, M.D., Ph.D., on accepting the new role as Vice Chair for Faculty Affairs. (4/2023)

Congratulations to Joanna Conant, M.D., on becoming the new Pathology Student Fellowship Director starting July 1, 2023. (4/2023)

Congratulations to The Cunniff Lab, on receiving funding to support research focused on malignant mesothelioma. The funding was from The Butler Family Foundation Fund for Cancer Research at the University of Vermont Cancer Center. The Butler Fund was established by the Butler family in memory of two loved ones lost to mesothelioma. (03/2023)

Congratulations to the following recipients that received pathology research support funding. Nathaniel Shannon in Brian Cunniff's, Ph.D., lab was awarded $1800 towards the cost of travel to the 2022 Annual Meeting of the Society for Redox Biology and Medicine (SfRBM). Litiele Cruz, Ph.D., and faculty mentor Albert van der Vliet, PhD., were awarded $2622 for her project "Characterization of Laminin Oxidative Modifications by Peroxidasin in Pulmonary Fibrosis". Nels Olson, PhD., MPH., $14,582 for the purchase of an Agilent BioTek 405 TS Touch Microplate Washer, Model 405 TSRS. Ashley Volaric M.D., Joanna Conant M.D., and David Seward, M.D, Ph.D., were awarded $13,680 for their project, "The Effect of Epstein Barr Virus Latency on Cellular DNA Methylation Profile of Diffuse Large B Cell Lymphoma". (3/2023)

A number of faculty and students from the pathology and laboratory medicine department presented research at the American Heart Associations Epidemiology, Prevention, Lifestyle, and Cardiometabolic Health (EPI/Lifestyle) Scientific Sessions 2023 in Boston February 28 - March 3. Students presenting were Maggie King, a master in science pathology degree student who was mentored by faculty scientist J. Peter Durda, Ph.D. pathology and laboratory medicine.  Maggie presented on "Complete Blood Count Analysis in the Risk Underlying Rural Areas Longitudinal (RURAL) Cohort Study with a Point of Care Instrument." Her study is supported by NHLBI. And second-year medical student and 2022 Cardiovascular Research Institute Summer Research Fellow Megan Zhou, mentored by pathology and laboratory medicine associate professor Nels Olson, Ph.D. Megan presented on  "Coagulation Factor IX and Incident Diabetes Risk: The Reasons for Geographic and Race Differences in Stroke (REGARDS) Study." Also, pathology and laboratory faculty members that were coauthors of presentations given, assistant professor Margaret Doyle, Ph.D., and University Distinguished Professor of pathology and laboratory medicine, Russell Tracy, Ph.D. (3/2023)

Congratulations to Dr. Bei Zhang, M.D., Ph.D., MLS(ASCP), associate professor of pathology and laboratory medicine, for being selected for a Distinguished Scholar Award by the Association of Biochemistry Educators for her submission entitled "Activate Students' Learning Outside Classroom". Dr. Zhang will be presenting this submission at the 2023 Association of Biochemistry Education Conference. (3/2023)

Congratulations to our 2023 Gender Equity Award Nominees. Gender Equity Champion Award nominee, Debra Leonard, M.D., Ph.D., Chair and Professor Pathology and Laboratory Medicine. Our departmental nominees for The Polaris Award for Outstanding Mentorship- an award for informal or formal mentorship for women or gender diverse college community members, Rebecca Wilcox, M.D., Pam Gibson, M.D., Yvonne Janssen-Heininger, Ph.D., and Christi Wojewoda, M.D. (2/2023)  

Congratulations to Dr. Scott Anderson, M.D., on being selected to receive the Association of Pathology Chairs 2023 Margaret Grimes Distinguished Achievement Award in Graduate Medical Education. This award was made in recognition of Dr. Anderson's outstanding contributions to graduate medical education and his stature as a nationally recognized leader in pathology education. (2/2023)

Congratulations to Dr. Yvonne Janssen-Heininger, Ph.D., Dr. Kelly Butnor, M.D., Dr. David "Bebo" Seward, M.D., Ph.D., and Dr. Sharon Mount, M.D., on their news story in The Charlotte News, on their "giant steps in cancer research." Read the full article here:   Humble Superstar (1/2023)

Congratulations to Dr. Elizabeth Bundock, M.D., Ph.D., Chief Medical Examiner of Vermont and clinical assistant professor of pathology, for her appointment by the American Board of Pathology, to the Test Development and Advisory Committee for Forensic Pathology 2023. (1/2023)

Dr. Beri Zhang, M.D., Ph.D., MLS(ASCP), associate professor of pathology and laboratory medicine, presented a panel, at the Snow Season Education Retreat, titled "The Pearls and Pitfalls of Publishing in Medical Education", with three clinicians Dr. Hale, Dr. Halle, and Dr. Rideout. (1/2023)

Congratulations to Dr. Bronwyn Bryant, M.D., assistant professor of pathology and laboratory medicine on her Awards for  Teaching and Educational Excellence, Learner Assessment, conferred at the Teaching Academy Induction and Award Ceremony on January 11, 2023. (1/2023)