UVM Cancer Center: Innovations Newsletter

THE UNIVERSITY OF VERMONT CANCER CENTER

R E S E A RC H / E D U C AT I O N / C O M M U N I T Y O U T R E AC H / C L I N I C A L C A R E

A CELL DIVIDES Genomic instability and cancer (Story on back cover)

WINTER 2022

INNOVATIONS

DIRECTOR’S MESSAGE Greetings!

I am thrilled to have joined the University of Vermont community as the new director of the UVM Cancer Center (UVMCC). I see tremendous potential for the center to use its key competencies to significantly reduce the burden of cancer and its impacts on society and our community.

The Cancer Center stands on four pillars that are a natural alignment of our core strengths and are prime areas for growth: 1) Research, 2) Education, 3) Community Outreach and 4) Clinical Care.

Our comprehensive research program includes basic laboratory studies on the mechanisms of cancer development: how genetic mutations drive cancer formation, for instance, or how complex tumor environments promote cancer growth and allow cancers to evade anti-cancer drugs.

It also encompasses population-based studies exploring areas like the environmental factors leading to the development of cancer; how best to detect cancer early when it can be most easily cured; and how to advance the treatment of patients through clinical trials.

The center’s educational activities deeply engage a range of audiences from undergraduate, medical, and graduate students to post-doctoral, clinical, and research fellows to junior faculty who are our next generation of cancer doctors and scientists.

The Cancer Center’s community outreach program ensures that its activities have direct impact on the populations we serve, identifying the critical cancer problems for the people of Vermont and northern New York, tailoring our programs to address these needs, and bringing solutions to reduce the burden of cancer directly to the community.

Compassionate clinical care addresses the needs of cancer patients by offering the highest quality of care by faculty physicians with unmatched expertise. Clinical care also focuses on providing support to patients and caregivers, tackling issues for cancer survivors, and identifying new methods to improve cancer care delivery.

The University of Vermont Cancer Center has substantial depth in each of these four pillars, which serve as the foundation for advancing the science and care of cancer and increasing its impact for patients, trainees, and the community at large. I am looking forward to working with UVMCC members, leaders at the University of Vermont and UVM Health Network, and community partners to lead the Cancer Center to even greater heights and attain even more comprehensive levels of excellence.

INSIDE 1 / Vision 2 / Community Outreach 3 / Research 4 / Education 5 / Clinical Care

University of Vermont Cancer Center 89 Beaumont Ave. Burlington, VT 05405

CONTRIBUTORS Kate Strotmeyer, Managing Editor Jeff Wakefield, Copywriter Ann Howard, Designer

Randall Holcombe, M.D., M.B.A Director, UVM Cancer Center Chief, Division of Hematology & Oncology, Department of Medicine UVM Larner College of Medicine

CONTACT INFORMATION UVM Cancer Center email@uvm.edu 802-656-3099 cancer@uvmcc.med.uvm.edu www.vermontcancer.org

UVM CANCER CENTER VISION The four pillars of the UVM Cancer Center—research, education, community outreach, and clinical care—facilitate transdisciplinary collaborations and implementation of our collective learning.

Working together, affiliated members, clinicians, scientists, and community stakeholders foster meaningful discovery for cancer patients and their caregivers and work to reduce the cancer burden in our region.

TRANSDISCIPLINARY COLLABORATIONS

COMMUNITY OUTREACH

COMMUNITY ENGAGEMENT

SCREENING & PREVENTION

DISCOVERY

EDUCATION

TRAINING & MENTORING

RESEARCH

CLINICAL TRIALS

CLINICAL CARE

IMPLEMENTATION & DISSEMINATION

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C O M M U N I T Y O U T R E AC H

THE COMMUNITY ADVISORY BOARD

brings together representatives from non-profit, government, and health organizations to inform the Cancer Center’s research, education, and community outreach initiatives.

Ultimately, the vision for the Community Advisory Board is bi-directional so that community members and Cancer Center leadership work side-by-side to reduce the cancer burden in our impact area. Newly-appointed members will meet for one hour on a quarterly basis beginning in March of 2022.

Community Advisory Board Members Dennis DePaul Executive Director Camp Ta-Kum-Ta Natalie Harder Community Member at Large Stephanie Jerome Co-Owner Visual Learning Systems Representative, Rutland-6 Vermont State Legislature Diane Jones Patient Navigator Central Vermont Medical Center Sarah Lemnah Executive Director Cancer Patient Support Foundation Sharon Mallory Comprehensive Cancer Control Program Coordinator Vermont Department of Health

Kirsten Murphy Executive Director Vermont Disabilities Council Justin Pentenrieder You First Program Manager Vermont Department of Health DiDi Remchuk Program Coordinator, Cancer Services Program of Northeastern NY Fitzpatrick Cancer Center Leigh Sampson Cancer Control Strategic Partnerships Manager American Cancer Society Rebecca Hewson-Stellar Nurse Navigator Southwestern Vermont Medical Center Olivia Sharrow Executive Director Vermont’s Free and Referral Clinics

Taylor Small Director of Health & Wellness Pride Center of Vermont Representative, Chittenden 6-7 Vermont State Legislature Donald Stevens Chief Nulhegan Abenaki Tribe Tom Torti Chief Executive Officer Lake Champlain Opportunity Fund Weiwei Wang Executive Director/Co-Founder Vermont Health Equity Initiative Andrea Villanti Deputy Director Rutgers Center for Tobacco Studies

MEMBER SPOTLIGHT Taylor Small is the Director of Health and Wellness for the Pride Center of Vermont. Taylor is a University of Vermont alum (2016) and through her position at the Pride Center of Vermont has been working to mitigate health disparities for LGBTQ+ Vermonters. Notably, her work in collaboration with the Vermont Department of Health has

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resulted in state-wide cancer screening campaigns, such as the award-winning “Got ‘Em, Screen ‘Em” campaign.

In 2020, Taylor was elected as a State Representative in the Vermont House, representing Winooski and Burlington. She is the first elected trans state representative in Vermont and the fifth in the nation.

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R E S E A RC H

RESEARCH LEADS TO FIRSTOF-ITS-KIND CLINICAL TRIAL OF MALIGNANT MESOTHELIOMA TREATMENT LINKED TO OCCUPATIONAL asbestos exposure, malignant mesothelioma (MM) is an aggressive cancer arising primarily from the outer lining of the lungs with a five-year survival rate of 5 to 10 percent. Since 2004, only two therapies have been approved for the treatment of MM, which affects about 3,000 people a year in the United States.

A promising new treatment for mesothelioma and metastatic cancer, arising from work in the laboratory of Brian Cunniff, Ph.D., a faculty member in the Larner College of Medicine Department of Pathology and Laboratory Medicine, is about to enter a Phase I clinical trial.

Bringing scientific discovery to a clinical trial is challenging. It takes about 20 years from discovery to clinical trials, and even then, only about 1 percent of potential new agents achieve FDA approval.

Bench to Bedside The new therapy developed at UVM had both prerequisites needed to crack that 1 percent: solid science and significant funding.

The innovative science, developed primarily by Dr. Cunniff, targets a universal vulnerability in cancer cells that can be exploited therapeutically.

“All tumor cells are reliant on efficient waste management systems to grow and survive; we’re interfering with those systems,” said Dr. Cunniff.

Collaborating with him on the research were Emeritus W W W.VERMONTC ANCER.ORG

BRIAN CUNNIFF AT HIS LAB

Professor Nicholas Heintz, Ph.D., and UVM alumnus Kheng (Newick) Bekdache, Ph.D. Ample funding soon followed this research discovery.

The pharmaceutical company RS Oncology wanted to fund a cure for MM and selected the UVM research as the vehicle to accomplish that. The company committed substantial funding to UVM for the comprehensive preclinical package.

Clinical Trial Over the last four-and-a-half years, Dr. Cunniff and his research team, in collaboration with researchers at Wake Forest School of Medicine and RS Oncology, have been directly responsible for showing the anti-cancer activity of the treatment approach they identified and in developing and testing a suitable formulation for delivery to humans.

This will be a ‘first in human’ trial to test the safety and activity of this novel approach in MM patients and will be subsequently considered as a targeted therapy for other cancers as well.

The clinical trial launched in England in late 2021, and the Cunniff Lab at the University of Vermont Cancer Center will serve as a primary site for translational research utilizing patient samples.

The work is at the heart of the UVM Cancer Center’s mission, according to director Randall Holcombe, M.D., M.B.A., who said “Bringing discovery from the laboratory into clinical trials where it can positively impact patients is what the UVM Cancer Center is all about.”

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E D U C AT I O N

SUMMER STUDENT RESEARCH PROGRAM TRAINS NEXT GENERATION OF CANCER SCIENTISTS WHEN SECOND-YEAR medical student Joaquin Reategui was looking for a research project last summer to complement and deepen his studies, options in the Covid-circumscribed world around him weren’t abundant.

Then a program in a Larner College of Medicine newsletter caught his eye.

The UVM Cancer Center Summer Student Fellowships in Cancer Research, Reategui read, was providing $3,000 stipends to graduate and medical school students for cancer-related research projects, overseen by senior faculty members affiliated with the center.

He promptly applied, was accepted and spent the summer analyzing the effectiveness of youth antivaping campaigns, working with his mentor, Andrea Villanti, Ph.D., then an associate professor of Psychiatry whose research focuses on how young adults’ beliefs about nicotine influence their perceptions of tobacco product addictiveness and harm.

Training medical doctors to do cancer research, in addition to graduate students and eventually undergraduates, is a key goal of the fellowship program. “Doctors often make good researchers,” said Randall Holcombe Holcombe, M.D., M.B.A., the center’s director, himself an M.D. with an active research portfolio.

“Since physicians have a lot of patient care experience, they have a keen perspective on how research will impact patient health,” he said.

In 2021, the program offered twelve students a broad spectrum of cancer research opportunities. Students worked with faculty mentors in disciplines ranging from

SUMMER 2021 RESEARCH AWARDEES Student: Alqassem Abuarqoub Mentor: James Stafford, Ph.D. (Neurological Sciences) Student: Rachel Bombardier Mentor: David Krag, M.D. (Surgery) Student: Amy Chang Mentor: Alissa Thomas, M.D. (Neurological Sciences)

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JOAQUIN REATEGUI

Surgery, Pharmacology, and Radiation Oncology to Biochemistry, Neurological Sciences and Pathology, and Laboratory Medicine, in addition to Psychiatry.

Reategui’s vaping project—which required him to master a data analysis program called Stata and bring meaning to a mass of data points in the youth surveys—sparked an interest in incorporating research into his career.

“I’m interested in the pediatric population, and I’ve been looking into oncology as one of the main paths to investigate with that population,” he said.

Student: Trevor Coles Mentor: Gary Stein, Ph.D. (Biochemistry) Student: Linda Cui Mentor: Nataniel Lester-Coll, M.D. (Radiation Oncology) Student: Sean Lenahan Mentor: David Seward, M.D., Ph.D. (Pathology and Laboratory Medicine) Student: Kiera Malone Mentor: Karen Glass, Ph.D. (Biochemistry) Student: Mikaela Mohardt Mentor: Brian Sprague, Ph.D. (Surgery)

Student: Allison Morrissey Mentor: Andrea Lee, Ph.D. (Microbiology and Molecular Genetics) Student: Joaquin Reategui Mentor: Andrea Villanti, Ph.D., M.P.H. (Psychiatry) Student: Kayla Sohl Mentor: Frances Carr, Ph.D. (Pharmacology) Student: Joshua A. Victor Mentor: Nimrat Chatterjee, Ph.D. (Microbiology and Molecular Genetics)

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AFTER LONG CLIMB TO RECOVERY, ONCOLOGY NURSE GIVES BACK WHEN KELLY GERNANDER finished an extensive chemotherapy regimen in 2007 and was declared cancer free, she felt on top of the world.

Less than a year later, Gernander—an oncology nurse in the UVM Cancer Center’s Hematology-Oncology Clinic —actually was, cresting the summit of Mt. Kilimanjaro with a group of rock musicians from The Fixx, Squeeze and the Stray Cats, many cancer survivors themselves.

The seven-day trip, which she applied for after seeing the fund- and awareness-raising annual event promoted on MTV, was “one of the best experience I’ve ever had, and one of the hardest,” Gernander said.

Doing hard things—she also ran a half marathon and conquered her fear of public speaking—was Gernander’s way of celebrating her victory over cancer. “I wanted to prove to myself I was back,” she said.

She hadn’t always felt so powerful. In the semester before graduating from nursing school at Johns Hopkins, she began experiencing GI symptoms. She thought she might have Crohn’s disease, as an uncle had, and went for a colonoscopy. The enterologist had an unwelcome surprise. She had bowel cancer.

After surgery at Hopkins, she came home to Burlington, where her parents lived, and opted to receive chemotherapy through the UVM Cancer Center, which offered the same state-of-the-art options as the celebrated Baltimore institution. “As a patient, it’s W W W.VERMONTC ANCER.ORG

CLINICAL CARE

KELLY GERNANDER REACHES THE PEAK OF MT. KILIMANJARO (LEFT), AND AT WORK IN THE CLINIC (BELOW)

comforting to know you’re getting the most current and best care,” she said.

Right Career By the time Gernander was diagnosed and treated, she was already set on becoming an oncology nurse. The impetus? The humane nursing care her mother received during treatment for breast cancer.

“I saw what a lifeline nursing can be for oncology patients,” she said.

Her own treatment at UVM confirmed she had made the right career choice. “I felt so connected to the nurses.

They took the time to get to know me and make the experience OK.” Gernander, who’s been an oncology nurse for 15 years, loves her work.

“You develop real relationships with patients quickly,” she said, “and have real conversations with them about what’s important in life.”

Since recovering, Gernander has been steadily giving back, running bone marrow drives at concerts and volunteering when she could.

“I had this great sense of purpose,” she said. “I was very grateful to still be alive and wanted to help others who were going through the throes of cancer.”

Last year she began facilitating the UVM Cancer Center’s Young Survivors Group, a support group she had joined during her treatment and where she drew great strength.

The advice she imparts to group members?

“We’ve been conditioned to grow up and think we can do everything on our own,” she said. “I tell them it’s OK to accept help. Friends are there for a reason.”

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University of Vermont Cancer Center 89 Beaumont Ave. Burlington, VT 05405 www.vermontcancer.org

GENOMIC INSTABILITY AND CANCER THE STUMPFF LAB, led by Larner College of Medicine Associate Professor of Molecular Physiology and Biophysics Jason Stumpff, Ph.D., uses advanced imaging approaches to investigate the cellular machinery controlling chromosome segregation during mitosis with the goals of gaining a better understanding of how the process works at the molecular level and identifying vulnerabilities within dividing tumor cells that could be leveraged for new cancer treatments. Accurate chromosome segregation depends on the mitotic spindle, a structure comprised of tube-like filaments, called microtubules (red in the image). The spindle microtubules are responsible for capturing, organizing, and then physically separating chromosomes into daughter cells during mitosis. Recent studies in the Stumpff lab have focused on elucidating the roles of specific molecules required for the formation and function of the mitotic spindle in both normal and tumor cells.

LUKE AWTRY PHOTOGRAPHY

This work, which has been supported by funding from the J. Walter Juckett Foundation, Susan G. Komen, and the National Institutes of Health, has revealed new mechanisms underlying cell division and identified a promising anti-cancer target for particularly aggressive breast and colorectal cancers.

STUMPFF LAB MEMBERS (LEFT TO RIGHT): JASON STUMPFF, CINDY FONSECA, KATIE QUEEN, CAROLYN MARQUIS, HANNAH POQUETTE, SARAH VANDAL, LESLIE SEPANIAC, KATIE SCHUTT, AND ALEX THOMPSON

ABOUT THE COVER

The image, taken by Cindy Fonseca, research assistant in the Stumpff Lab, shows a human cell undergoing mitotic division. Mitosis is a fundamental process that involves the equal segregation of replicated genomic material from one cell into two new “daughter” cells. Mitosis is required for both human development and maintenance, and it is estimated that within an adult human body, trillions of cell divisions occur daily. Mistakes in mitosis can lead to missegregation of genetic material, which is packaged into chromosomes (blue in the image), and the formation of daughter cells with too many or too few chromosomes. This state, called aneuploidy, is a hallmark of cancer cells and contributes to tumorigenesis.

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