Dear Program in Cancer Biology Members,

It was with some trepidation and plenty of enthusiasm that I stepped into the role of Director of Graduate Studies this fall, and I have loved every second of it! The best part has been getting to know our graduate students better. We have amazing trainees in our program! They are conducting cutting-edge scientific research and are wonderful people. What more could you ask for?

In the hustle and bustle of the holiday season, I hope faculty and trainees alike take a moment to rest, relax, and recharge. It has been wonderful to see so many colleagues and trainees from our program at the Cancer Biology annual retreat and holiday party (many thanks again to our CBSA for organizing these events!) and to reconnect with so many of you. I hope you all enjoy your time with family, friends, or in solitude this holiday season, and I look forward to seeing you all in the new year!

Gratefully,

Rachelle Johnson

Faculty Spotlight:

Jason R Schwartz, MD, PhD
Assistant Professor of Pediatrics Hematology/Oncology

Dr. Schwartz’s research studies seek to understand the molecular mechanisms and pathogenesis underlying pediatric myelodysplastic syndromes (MDS), specifically those syndromes caused by germline mutations in SAMD9 and SAMD9L. His current focus is to better understand the biological consequences of SAMD9 and SAMD9L mutations in MDS through genomic and functional investigations in an induced pluripotent stem cell (iPSC) model system of pediatric MDS. This iPSC model system was developed through CRISPR/Cas9 knock-in of known pathogenic SAMD9 or SAMD9L mutations at the respective endogenous locus. Using additional CRISPR tools, Dr. Schwartz is working to selectively activate or repress transcription of these loci and interrogate differential expression patterns that result using RNA sequencing. These studies will help to uncover the important cellular functions of these two interesting genes. Additionally, Dr. Schwartz hopes to describe the mechanisms and clonal evolution that underlie the SAMD9/9L-mediated development of monosomy seven and, in some patients, subsequent spontaneous hematopoietic recovery through single-cell multi-omics. The knowledge gained from a deeper understanding of how SAMD9/9L mutations and chromosome 7 loss effects hematopoiesis and how these lesions clonally evolve over time will lead to the ability to surveil patients with predispositions to develop MDS/AML deeply. Thus, this results in the ability to predict which patients may not need bone marrow transplant (particularly some of those patients with germline SAMD9/9L mutations) but also identify which patients are at the highest risk of AML development such that transplant can occur prior to the development of malignancy. Please join us in welcoming Dr. Schwartz to the Program in Cancer Biology!
View Publications on PubMed

Postdoctoral Fellow Spotlight:

Sarah Maddox Groves, PhD
Postdoctoral Researcher (Quaranta Lab)
Chemical and Physical Biology Program

Dr. Maddox finished her PhD in March of this year and has continued her research in the Quaranta lab as a post-doc. She is a systems biologist and has built a gene regulatory network model for understanding Small Cell Lung Cancer, an incredibly recalcitrant form of cancer. In SCLC, one of the biggest problems is the high rate of relapse, caused by the ability of the tumor to shape-shift after treatment to a new identity that can better handle therapy. Because cell identity is controlled by a network of transcription factors that interact dynamically, cells can learn to respond to treatment by turning on and off different gene programs that make them harder to kill. Dr. Maddox has developed a computational network algorithm and data-driven analysis methods that simulate these changes to predict how cells that survive treatment will evolve. When not working, she enjoys cooking, baking, writing, and hiking with my husband, Matthew and dog, Millie.

Graduate Student Spotlight:

Pawan Bhat is a PhD candidate in the Ferrell lab, studying the progression of clonal hematopoiesis of indeterminate potential (CHIP) to hematologic malignancy. CHIP occurs in individuals with hematologic malignancy-associated mutations, though these individuals lack the diagnostic criteria for malignancy. One driver of CHIP disease progression is inflammation, which includes dysregulated innate immune signaling in CHIP cells. However, the role of inflammatory signaling in human CHIP remains largely unexplored. To address this gap, he investigated human CHIP peripheral blood samples for inflammatory-related gene signatures in close collaboration with the Bick lab. As a result, he discovered that dysregulated innate immune signaling is a cell-intrinsic property of CHIP monocytes and that these monocytes are hypersensitive to the pro-inflammatory cytokine IL-6. His work is currently featured in a bioRxiv article which you can read here. In future studies, he aims to investigate the regulatory dynamics of CHIP immune signaling networks in longitudinal patient samples, especially in samples that have progressed to malignancy. Pawan enjoys reading, traveling, teaching yoga, and participating in cultural activities outside the lab. Read article here

The 22nd Annual Retreat for Cancer Biology was held on December 5th at the Adventure Science Center

The Host-Tumor Interactions Program, the Cancer Cell Biology Program  and the Program in Cancer Biology hosted the annual student led retreat for Cancer Research. The retreat highlighted an outstanding patient advocate presentation from Randi Semrick; her patient perspective is critical to the research we strive to do. Hearing from distinguished researchers reminds us of the impact we aim to have in the clinic. The fundraising effort and silent auction were a success, and all proceeds will be donated to the Gilda’s Club of Middle Tennessee. A very special thank you goes out to all the vendors and individuals who contributed to the auction, a total of $2,000 was raised to benefit Gilda’s Club!!!
The keynote speaker for this year’s retreat was Ned Sharpless, MD. Dr. Sharpless is an eminent oncologist and leader in cancer research, best known scientifically for his research in cellular aging, senescence, circular RNAs, and the cell cycle. Dr. Sharpless held the Welcome Distinguished Professorship of Medicine and Genetics at UNC Lineberger Comprehensive Cancer Center, where he later became Cancer Center Director. He was then named Director of the National Cancer Institute, a position he held for five years, during which he served as Acting Commissioner of the Food and Drug Administration. Dr. Sharpless has an outstanding publication record, being cited over 40,000 times. This year, Dr. Sharpless was named to the National Academy of Medicine for his exceptional contributions to the field of cellular aging.

The Best Post-doctoral Fellow Presentation was awarded to:

Katie M Young, PhD
(Reinhart-King Lab)
Postdoctoral Researcher, Biomedical Engineering.

Genome-scale CRISPR Knockout System to Explore Geno mechanical Relationships in Metastatic Cells.

The Best Graduate Student Presentation was awarded to:

Amanda B. Hesterberg
IGP Graduate Student
(Hurley Lab)

Asporin (ASPN)+ Cancer-Associated Fibroblasts Activate HER2/HER3 Signaling and Promote Prostate Cancer Progression.

The Best Graduate Student Poster Presentations were awarded to:

Emilie Fisher, MSTP
(J Rathmell Lab)

Improving anti-tumor CD8+ T cell function through manipulating glutamine metabolism.

Matthew Loberg, MSTP
(Weiss Lab)

Unique Stromal Infiltrate Defines Aggressive Thyroid Cancers.

Honorable mention for the Best Graduate Students Poster Presentations were awarded to:

Brandie Taylor, MS
(Balko Lab)

Overcoming MHC-I Heterogeneity in Immunotherapy Resistant Breast Cancers via NK Cell Activation.

Kara McNamara, IGP Graduate student
(Wilson Lab)

Polyamine Dysregulation during Helicobacter pylori Infection and its Impact on Gastric Carcinogenesis.

Sarah Reed, MSTP
(Park Lab)

Investigating the Impact of Clonal Hematopoiesis on Solid Malignancies.

Program in Cancer Biology Faculty and Trainee News and Research:

Metastasis Research Society (MRS), the 19th Biennial Meeting (2022), was held in Buenos Aires, Argentina. The MRS is dedicated to promoting the furtherance of research into all aspects of metastasis and the exchange of metastasis-related information amongst all key stakeholders in metastasis research and treatment, including scientists, clinicians, and patients.
Our PhD trainees presented their research internationally in Buenos Aires, Argentina!!  “The Influence of Sex on the Immune Microenvironment of Female Breast Cancer”, research was presented by Ebony Hargrove-Wiley and  “Investigating the Role of Type II IL4 receptor in Breast Cancer Brain Metastasis”, was presented by Wendy Bindeman.

Pictured above are Ebony Hargrove-Wiley and Wendy Bindeman, IGP Graduate students from the Fingleton Lab and Deronisha Arceneaux from the Lau Lab, they visited a neighborhood in Buenos Aires and enjoyed the local cuisine for lunch.

Hong Yuen Wong PhD,
Amanda B Hesterberg IGP Graduate student, Jeffrey C Rathmell PhD, Adam X Miranda IGP Graduate student, Paula J Hurley PhD, Ben H Park MD, PhD, Sarah Croessmann PhD, Brenda L Rios IGP Graduate student.

Single-cell analysis of cribriform prostate cancer reveals cell-intrinsic and tumor microenvironmental pathways of aggressive disease. The study presents a compendium of information on cancer and TME cells in prostate ICC/IDC. Our findings support that ICC/IDC has an aggressive phenotype by upregulating the TNFα pathway via the NFκB pathway leading to the expression of JAG1, which likely induces neovasculature through NOTCH signaling. In addition, we show that the ICC/IDC TME is immunosuppressed, resulting in less dysfunctional T cells and increased M2 C1QB+TREM2+APOE+ macrophages.

Margaret Axelrod PhD,  Ann Hanna PhD,  P. Brent Ferrell PhD,  Susan Opalenik PhD, Brandie C Taylor MS BS,  Xiaopeng Sun BS,  Jeffrey C. Rathmell PhD,  Justin M Balko PharmD, PhD

T cells specific for α-myosin drive immunotherapy-related myocarditis

The researchers discovered that T-cells recognizing the cardiac antigen α-myosin are the mechanism for this complication, setting the framework to identify biomarkers so at-risk patients can be recognized and medical strategies developed for them to tolerate the immunotherapy. Their findings were reported on November 16 in Nature.

While cancer of the appendix is rare, for a small percentage of patients, the disease may be linked to a particular genetic variant, a new study from the lab of Andreana Holowatyj, PhD, MSCI, suggests. Researchers built on earlier research with this study, finding that 1 in 10 people with cancer of the appendix carries a genetic variant associated with cancer predisposition. “Based on these data, we can recommend genetic counseling and multi-gene panel testing of cancer susceptibility genes for all appendix cancer patients, regardless of age or family history of cancer,” said researcher Andreana Holowatyj. She is an Assistant Professor of Medicine and Cancer Biology at Vanderbilt University Medical Center. The findings were published on November 11 in the journal JAMA Oncology and presented simultaneously at the 2022 Collaborative Group of the Americas Inherited Gastrointestinal Cancer (CGA-IGC) annual meeting in Nashville.

 Julie Rhoades, PhD is a newly elected member of the Board of Directors for the Cancer Biology Training Consortium (CABTRAC)!

In Memory of: The MOURNERS KADDISH

When I die, Give what’s left of me away to children and old ones.

And when you need me, put your arms around anyone and give them what you need to give me. I want to leave you with something better than words or sounds. Look for me in the people I’ve known or loved,

and if you cannot give me away, at least let me live on in your eyes and not in your mind. You can love me most by letting hands touch hands,

bodies touch bodies, and letting go of children that need to be free. Love doesn’t die; people do. So, when all that’s left of me is love, give me away.

Albert “Al” Reynolds, PhD, a celebrated and respected Professor Emeritus in the Department of Pharmacology, passed away in early November. As we continue to try to process the terrific loss of our colleague, friend, and/or mentor, we are interested in establishing a Fund in Al’s honor that would be used to benefit trainees in Cancer Biology. Training and inspiring students and postdoctoral fellows was a driving force for Al, so this seems to be a fitting way to honor him.  In talking with the Vanderbilt Development office, we have established a way for you to give to this fund online by making a contribution to the Department of Pharmacology through a subaccount established in Al’s memory.  You may access this account by clicking on vu.edu/pharmacologyfund.  If this is something on your heart that you would like to support, please respond by indicating the amount you can pledge so that we can determine the feasibility of establishing the Al Reynolds Foundation Fund for Cancer Biology trainees. Thank you for your consideration.

R. Daniel Beauchamp, MD, the John Clinton Foshee Distinguished Professor of Surgery and Cell and Developmental Biology at Vanderbilt University School of Medicine, former Chair of the Section of Surgical Sciences (2001-18), and former Surgeon-in-Chief at Vanderbilt University Medical Center (2001-18), died on November 27, 2022, at Alive Hospice. His significant roles in the Vanderbilt-Ingram Cancer Center included Deputy Director (2011-19) and Co-Director of the GI oncology program (2014-22). Read Dr. Beauchamp’s professional biography and details of his almost 30-year career at Vanderbilt detailing the tremendous impact he had on the lives of his patients, colleagues, and community members.

“You give but little when you give of your possessions. It is when you give of yourself that you truly give.”– Kahlil Gibran
Have you received an award, a paper published or any other good news you would like to celebrate with our community? If so, please e-mail: kerry.w.vazquez@vanderbilt.edu.
Newsletter header photo credit to Dr. Anna Vilgelm, “DNA Comets.”  Articles and Pictures credit to VU and VUMC. Dan Beauchamp credit Anne Rayner; holiday pictures credit to Unsplash. Dr. Schwartz photo by Donn Jones/VUMC. Andreana Holowatyj article, By Cara Murez Health Day Reporter from US News and world report.