In mid-September each year, we greet the fall season with the arrival of the fall equinox (otherwise known as the autumnal equinox). This is the moment when the Sun crosses the Equator, and we will begin to see more darkness than daylight. Whether it has been chilly for weeks or there are still balmy summer-like temperatures, this is the start of astronomical fall.

Make time for yourself in nature this fall; the stress of a global pandemic while working long hours can be overwhelming. Middle Tennessee has much to do in the city and beautiful hiking trails and greenways to enjoy during this season. Be well and practice self-care.

Getting to know you:
Faculty Spotlight:

James R. Goldenring, MD, PhD

Professor of Surgery
Professor of Cell and Developmental Biology
Vice Chair, Surgical Research
Paul W. Sanger Professor of Experimental Surgery.

Please join us in welcoming Dr. Goldenring to The Program in Cancer Biology!

Dr. Goldenring’s research spans multiple topics across the broad area of epithelial biology. He has been a leader in investigating the roles of specific Rab small GTPases and their effectors in regulating vesicle trafficking, membrane recycling, and cell polarity. His recent studies are focused on the role of small GTPases in the initiation of gastrointestinal cancers. In addition, he is studying the specific defects in apical vesicle trafficking in the etiology of neonatal diarrhea syndromes in humans. His recently published work defined the role of Rab11a and Rab8a interactions with myosin Vb in the development of severe neonatal diarrhea in children with Microvillus Inclusion Disease. In addition, he has recently published work on the phenotypes of mouse models of MYO5B KO. The laboratory is now analyzing the newly developed mouse models for targeted loss of MYO5B, Rab11a and Rab11-FIP2 in the intestines and other organs. Other work in the Goldenring laboratory is defining the role of Par1b/MARK2 phosphorylation of Rab11-FIP1 and Rab11-FIP2 on the establishment and maintenance of polarity. These studies utilize phospho-specific antibodies as well as Rab11-FIP mutants to define defects in trafficking and polarity. Finally, Dr. Goldenring’s laboratory is also investigating the role of Rab25 as a tumor suppressor in the colon using the Rab25-/-;Smad3+/- mouse model, which develops spontaneous invasive distal colon cancers. He is studying the mechanisms responsible for the development of pre-neoplastic lineages from metaplasia in the stomach and their role in gastric carcinogenesis.

Trainee Spotlight:

Tolu Omokehinde, PhD Candidate.

Tolu is the first author of an article published in the Journal of Bone and Mineral Research, entitled “gp130 cytokines activate novel signaling pathways and alter bone dissemination in ER+ breast cancer cells.” The lab of Rachelle Johnson, PhD focuses on breast cancer metastasis to bone and breast cancer dormancy in bone, with an emphasis on the signaling pathways that mediate these processes. Tolu’s research explores and characterizes the function of the gp130 cytokines in several breast cancer cell lines and patient datasets by highlighting the relative expression of the gp130 ligands and cytokine specific receptors, identifying novel signaling pathways activated by the cytokine family, and assessing the in vivo outcomes of breast cancer bone colonization following overexpression of the gp130 ligands OSM and CNTF. His data indicate that all of the cytokines and receptors that are required for autocrine or paracrine OSM, LIF, and CNTF signaling are present in all breast cancer subtypes at the transcript level; however, expression of the receptors (LIFR, OSMR, CNTFR, and gp130) is considerably lower in ER- compared to ER+ disease, suggesting that loss of the gp130-related receptors (not just LIFR, as previously reported), may be associated with more aggressive disease. In addition, analysis of in vitro and patient data indicate that the gp130 ligand OSM promotes spontaneous dissemination to the bone, while CNTF may have the opposite effect. Collectively the data highlight the nuances of LIFR signaling in breast cancer and indicate that future targeting of the pathway will need to focus on the individual ligands rather than the receptor.

Staff Spotlight:

Kimberly D. Turner, MBA

Kim began her career as a research administrator at Meharry Medical College; as a Financial Analyst, she managed a small portfolio of grants in the central grants office for five years. Since joining Vanderbilt University 15 years ago, she has served in many areas and capacities. Her passion for solving challenging problems and advancing her career has benefited Vanderbilt. Kim has worked as a center administrator for the Department of Human Genetics, the HR officer for Basic Sciences Research Administration, Pod 3, and now in the position as a post-award role in Cancer Biology Education, Pharmacology, and Neuroscience.
Even though Kim is not a researcher, she feels her many contributions in managing grants help the faculty with their science and discovery. In addition, Kim love’s that she can give financial guidance on grants, whether it be on a large R01 or helping a student with their fellowship. She is currently supporting thirty-seven PI’s and around 153 projects, totaling roughly $30M!
Kim received her undergraduate degree in Business Administration from Tennessee State University and a MBA from Bethel University. As a Nashville native, a rare find these days, she enjoys her home town. In her spare time, Kim loves spending time with family, traveling, going to the movies, and watching all things sports. 

Program in Cancer Biology Trainees Research:

Kara McNamara, BS

Kara is a third-year graduate student in the Program in Cancer Biology and has published a first author review in Nature Oncogene titled,  “The role of polyamines in gastric cancer.” The Wilson lab focuses on the host response to the gastric pathogen Helicobacter pylori and how infection can lead to gastrointestinal mucosal inflammation and carcinogenesis. Specifically, the lab studies polyamine molecular and cellular functions to investigate ways to target polyamine metabolism for anticancer therapeutic benefit. Kara’s project focuses on the role of the polyamine, spermidine, in H. pylori-induced gastric cancer. Originally from Worcester, Massachusetts, she attended the University of Massachusetts Amherst and graduated in 2019 with a BS in Biochemistry and Molecular Biology. She joined the IGP program the following year and subsequently joined the lab of Dr. Keith Wilson. Kara enjoys trying new coffee shops, hiking with friends, and exploring local festivals outside of the lab.

Clayton Marshall, PhD

As a postdoctoral trainee in the Pietenpol lab, Dr. Marshall recently published a first-author paper report in Cell Death & Disease.

The research discovered that proteins p63 and p73, members of the p53 family, regulate cell differentiation, proliferation and death. The p53 family signaling network is the most frequent target of mutations in human cancers. Analyzing p63 and p73 functions have been challenging because multiple isoforms of each are expressed and can interact to regulate target genes. The researchers analyzed 36 human tissues and quantified p63 and p73 isoform expression using GTEx (Genotype-Tissue Expression) project data. They found coordinate expression of p63 and p73 in basal cell populations of epithelial tissues, with the alpha isoforms predominant in nearly all tissues. They also identified a previously unreported p73 mRNA product. The findings support future investigations of p63 and p73 in concert since they are so often co-expressed. Dr. Marshall has recently transitioned to a new role at the Vanderbilt Ingram Cancer Center as a senior program manager.

Vera Mayhew Todd, PhD and Miranda Sowder Clements, PhD are recent graduates from the Program in Cancer Biology, and have had two publications accepted in August 2021! The first paper was recently accepted by Communications Biology titled, “Hypoxia-inducible factor signaling in breast tumors controls spontaneous tumor dissemination in a site-specific manner”. The second paper published in Oncogene  entitled, “HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer”, discusses that despite advances in breast cancer treatment, residual disease driven by dormant tumor cells continues to be a significant clinical problem. In addition, leukemia inhibitory factor receptor (LIFR) promotes a dormancy phenotype in breast cancer cells, and LIFR loss is correlated with poor patient survival. They demonstrate that histone deacetylase inhibitors (HDACi), which are in phase III clinical trials for breast cancer, epigenetically induced LIFR and activated a pro-dormancy program in breast cancer cells. In addition, HDACi slowed breast cancer cell proliferation and reduced primary tumor growth. 

Dr. Clements is currently a Postdoctoral Researcher at the National Cancer Institute, working on characterizing stromal cell populations in the pre-metastatic niche and their role in tumor progression and metastasis, emphasizing the bone microenvironment. In addition, Dr. Todd recently accepted a position at Belmont University as a Lecturer.

Ann Hanna, PhD
Postdoctoral Research Fellow (Balko Lab)

Dr. Hanna recently published a review article in Breast Cancer Research and Treatment, titled, “Breast Cancer resistance mechanisms: challenges to immunotherapy.”  The clinical implementation of immunotherapy has profoundly transformed cancer treatment. Targeting the immune system to mount anti-tumor responses can elicit a systemically durable response. Employing immune checkpoint blockade (ICB) has suppressed tumor growth and vastly improved patient overall and progression-free survival in several cancer types, most notably melanoma and non-small cell lung carcinoma. Despite the widescale clinical success, ICB response is heterogeneously efficacious across tumor types. Many cancers, including breast cancer, are frequently refractory to ICB. This review discusses the challenges facing immunotherapy success and addresses the underlying mechanisms responsible for primary and acquired breast cancer resistance to immunotherapy.

CANCER BIOLOGY STUDENT ASSOCIATION EXECUTIVE BOARD MEMBERS

The Program in Cancer Biology Student Led Retreat is December 2, 2021.

The CBSA is planning the retreat this year and Dr. Padma Sharma from MD Anderson has agreed to be the guest speaker! We hope to have the event in person. Let us welcome our 2021-2022 CBSA officers who are working hard for our program’s success. Top L-R: Bottom L-R:

Carlos Detres Roman, BS – Treasurer (Philip Lab)

Ebony Hargrove Wiley, BS – Academic Chair (Fingleton Lab)

Kara McNamara, BS – Social Chair (Wilson Lab)

Brandie Taylor, MS, BS – Communications Chair (Balko Lab)

Amanda Hesterberg, BS – Philanthropy Chair ( Hurley Lab)

Brad Davidson, BS – Executive Chair (Park Lab)

Wendy Bindeman, BA – Philanthropy Chair ( Fingleton Lab)

READING SUGGESTIONS FROM THE ANTI-RACISM BOOK CATALOG

RECENT ACTIVITIES OF THE CANCER BIOLOGY DEI COMMITTEE:

Rachelle Johnson PhD, led the development of two sponsored lecture series featuring URM faculty:
1)  Avery D. Posey PhD, Assistant Professor, Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine.
2) Dineo Khabele MD, Professor and Chair of the OB/GYN Department at the University of Kansas.

The DEI Committee sent out a survey to evaluate faculty and trainee interest in various activities that would promote diversity, equity and inclusion.

Dana Brantley-Sieders PhD, Brenda Rios BS and Courtney Edwards BS, are developing more opportunities around alternative career training. They plan to have a seminar series featuring former Vanderbilt trainees, from diverse backgrounds, with student-led informal discussions on the speaker’s personal and professional path to their current position.

Julie Rhoades PhD and Marjan Rafat PhD are working on developing and distributing ongoing DEI training opportunities. 

The DEI is planning and developing more volunteer opportunities and mentoring networks, please reach out and join our team.  Also, if you would like more information about the DEI library that has been established, please contact Rachelle.Johnson@vanderbilt.edu. 

Keith T Wilson, MD, Thomas F. Frist, Sr. Chair in Medicine, Professor of Medicine, Professor of Pathology, Microbiology and Immunology. Director, Center for Mucosal Inflammation and Cancer.

Dr. Wilson’s laboratory is focused on gastrointestinal mucosal inflammation and carcinogenesis. This includes the innate immune response in macrophages and the identification of ways that this response is ineffective. They have also elucidated mechanisms whereby epithelial responses are inappropriate, leading to risk for cancer development. Dr. Wilson and his collaborators recently published their research findings in Oncogene, which discusses, ”Ornithine decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus”.  The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. They studied 94 variants in 54 human genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoro-methyl ornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. The main findings were that the ODC1 variant rs2302615 was associated with gastric cancer (odds ratio = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. In addition, the ODC1 SNP association with gastric cancer was stronger in individuals who carried a TLR4 polymorphism. It was concluded that the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials focused on inhibition of ODC.

Richard M Peek, Jr., MD
is the director of the Division of Gastroenterology, Hepatology, and Nutrition, The Mina Cobb Wallace Chair in Immunology, and Professor of Medicine and Pathology, Microbiology and Immunology at Vanderbilt University Medical Center. His research focuses on the molecular origins and pathways that regulate inflammation and induced malignancies in cancer. Read about his research and break through discoveries in Gastric Cancer and IBC here.

RECENTLY DEPARTED FACULTY:

Sergey V Novitskiy, MD, PhD
Adjunct Associate Professor in the Department of Medicine has worked at Vanderbilt University for 17 years and has started a new career in Industry. His team at Amgen (South San Francisco) works on Immuno-Oncology, founded in 1980 as Applied Molecular Genetics; Amgen’s current specialty is human therapeutics. Historically, some of Amgen’s most successful drugs–Neupogen, Prolia, Vectibix, among others–have been used to treat low white blood cell counts, osteoporosis, and colorectal cancer, respectively. Please reach out to Dr. Novitskiy (sergey.v.novitskiy@Vanderbilt.Edu) if you are interested in joining the Amgen team.

Aron Parekh, PhD
Assistant Professor of Otolaryngology – Head and Neck Surgery and Biomedical Engineering.
The Program in Cancer Biology wishes Dr. Parekh success in his new position at Susan G Komen as the Scientific Program Manager. Dr. Parekh’s unique talent and scientific expertise have been a gift to Vanderbilt and our colleagues. Thank you for your contributions to the Program in Cancer Biology!

Program in Cancer Biology Lab Highlight

This month we wish to highlight Justin Balko’s lab and the many accomplishments and hard work from his team members.

Pictured L to R: Ann Hanna, PhD, Elizabeth Wescott, Abbey Toren, Justin M. Balko, Pharm.D, PhD, Derek Franklin, PhD, Susan Opalenik, PhD, Maggie Axelrod, MSTP, Jamaal James, PhD.

The BALKO LAB  studies how to make immunotherapy work better – this includes identifying the patients who will most likely benefit; testing new combinations that expand benefit to more patients, and finally, identifying biomarkers and mechanisms of toxicity to immunotherapy so we can mitigate risk in the clinic. We focus on improving treatment outcomes in breast cancer (particularly triple-negative breast cancer) as well as in other solid tumors through translational approaches. To accomplish this, we integrate data from genomic and molecular profiling studies with molecular biology and signal transduction methodologies to identify altered pathways in cancer, the functional consequences of these alterations, and ways to directly target them in patients to improve clinical outcomes and survival. These efforts span in silico (publicly available databases), in vitro (cell culture), in vivo (mouse and human clinical studies) and in situ (histology) methods.

Meet the Balko Lab Cat!  Since they can’t (and don’t) have real animals in the lab, this one is a robot cat, and she is always dressed appropriately for each season.

Send Us Your News

Have a suggestion, announcement or event  you want to share with the Cancer Biology community? Please E-mail:kerry.w.vazquez@vanderbilt.edu
Newsletter header photo credit to Dr. Anna Vilgelm, “DNA Comets”. Photo and article credit to VU and VUMC. Fall foliage picture and partial write up credit the farmers almanac.com. Clayton Marshall article credit to Leigh MacMillan. Cancer cells picture credit to the NIH and Roger Chalkley -Vanderbilt.