Dr. Jennifer Richer, Professor of Pathology and Co-Leader Tumor Host Interaction Program, University of Colorado Cancer Center -has studied steroid hormone receptor action in women's cancers for over 25 years. Recent studies from her laboratory demonstrated that in addition to receptors for the "female" hormones estrogen and progesterone, androgen receptors (AR) play an important role in breast cancer. Her laboratory also focuses on alterations in non-coding RNA in breast and gynecologic carcinomas that lead to aberrant expression of embryonic, non-epithelial proteins including immune suppressive factors reminiscent of those made by trophoblasts to achieve fetal tolerance. Dr. Richer is a standing member of the NIH Tumor Cell Biology study section and has served on grant review panels for the American Association for Cancer Research, Department of Defense Breast Cancer Research Program and Susan G. Komen Foundation. She co-chaired the Keystone Symposium on Nuclear Hormone Receptors in 2016 and served on Annual Meeting Organizing committees for the Endocrine Society and AACR. In addition to serving on advisory boards for the Cancer League of Colorado, MD Anderson Uterine Cancer SPORE and the University of Texas at El Paso College of Science Advisory Board, she served on scientific advisory boards for Medivation, Bayer, Orion, and Innocrin. Dr. Richer is highly invested in the success of young trainees in the University of Colorado Cancer Center and the Cancer Biology Graduate Program. In 2015 she received the Dean's Mentoring Award and the NIH Broadening Experiences in Scientific Training (BEST) Faculty Sponsor Awards from the Graduate School and along with John Tentler, PhD, Co-directs the University of Colorado Cancer Center's American Cancer Society Institutional Research Grant that funds cancer research pilot projects conducted by junior faculty
Bryan Mitton, MD, PhDBryan Mitton, MD, PhD grew up in Mississippi and received his B.S. in Cell and Structural Biology from the University of Illinois Urbana-Champaign. He then pursued combined medical and research training at the University of Cincinnati College of Medicine through the Medical-Scientist Training Program (MSTP). He earned his Ph.D. in 2007 in the Department of Pharmacology and Cell Biophysics, and his M.D. in 2008. He completed clinical residency training in Pediatrics at the University of California, Los Angeles in 2011, and is currently a Hematology-Oncology Clinical Fellow of Pediatrics at the Lucile Packard Children's Hospital at Stanford University. He has worked in the laboratory of his advisor, Dr. Kathleen Sakamoto, MD, PhD, since 2010.
Dr. Mitton's primary research interest is in discovering new therapies for high-risk leukemia. In children, leukemia is the most common form of cancer, and unfortunately, cure rates for both children and adults with Acute Myelogenous Leukemia (AML) remain close to 50%. Previous work had shown that 'CREB', a signaling molecule in cells which facilitates cell growth and survival, is elevated and overactive in AML cells compared to normal cells; CREB levels are increased most in patients with high-risk AML, and it therefore also serves as a marker for patients with a poor prognosis. Thus, Dr. Mitton's research focuses on discovering new drugs that block CREB function. One promising drug designed to block CREB was able to reduce AML cell growth by 80% in a mouse model when used alone; importantly, this compound did so without any toxic effects on the mice studied. This drug also killed cultured AML cells but was not toxic to normal human bone marrow cells, suggesting that CREB inhibition may represent an effective, specific and safe treatment for AML.
Much work remains to be done in characterizing the overall role of CREB in AML, and how well a CREB-inhibiting drug may work in combination with standard chemotherapy. Dr. Mitton's project , Targeting the CREB Proto-Oncogene for Acute Myelogenous Leukemia , will begin to answer these questions. If successful, Dr. Mitton's work could result in the discovery of a new class of drugs for treating AML in children and adults and address an important clinical problem.
Ryan W. Honaker, PhDRyan W. Honaker, PhD grew up in Utah and received his B.S. in Microbiology from Brigham Young University. After several years working in the Bay area, where he met his wife, he attended the University of Colorado Denver, earning his PhD from the department of Microbiology as he studied the genetic mechanisms Mycobacterium tuberculosis uses to adapt and cause latent disease.
Dr. Honaker became interested in the interaction between bacteria and the host, and the resulting diseases that can be caused by this interaction. He and his wife both missed the Bay area. Thus, in 2010 he joined the laboratory of Dr. Manuel Amieva at Stanford University to pursue the study of the bacterium Helicobacter pylori , the only known cancer-causing bacteria. This enabled Dr. Honaker to combine his knowledge of bacteria with his interest in the interaction between bacterium and host to study cancer, which had sadly become more personal with the untimely death of his brother-in-law from the disease.
The goal of Dr. Honaker's research is to better understand how Helicobacter pylori (Hp) causes stomach cells to become cancerous. Gastric cancer is an important worldwide public health concern, second only to lung cancer in the number of yearly deaths it causes. Hp is the most important known risk factor for gastric cancer development, and strains of the bacteria that directly inject a specific protein named CagA into human cells cause more severe disease. Dr. Honaker's work will lead to a better understanding of the interaction between Hp and human cells, specifically focusing on the hypothesis that, in the stomach, CagA may be directly injected into proliferating precursor cells and possibly stem cells (which normally allow for healthy turnover of the cells in the lining of the stomach). Dr. Honaker will determine how injection of this protein alters the normal growth and differentiation activities of these cells and how this leads to cancer.
Many aspects of gastric cancer are currently unknown. Dr. Honaker's investigation, entitled, The Role of Helicobacter Pylori Epithelial Interactions in Cancer , will identify critical steps in stomach cancer development and will increase our abilities to prevent, detect, and treat this disease. Since evidence is growing that bacterial populations in the intestine may also play a role in the development of colon cancer, Dr. Honaker's work could also help us better understand this type of cancer.
Terry R. Medler, PhDTerry R. Medler, PhD grew up in Marseilles, Illinois and received his B.S. in Chemistry and Biology at Valparaiso University. He then moved to The Johns Hopkins University to pursue his interest in medical research and also received his M.S. in Biotechnology from Hopkins. After deciding that a career in research was his aspiration, he moved to Chicago to pursue his Ph.D. in Cancer Biology at Northwestern University.
The realization that cellular programs in tumor cells alone are not sufficient to drive and sustain tumor growth brought him to the laboratory of Lisa M. Coussens, Ph.D. at Oregon Health & Science University. Her lab has pioneered groundbreaking research showing that tumor growth is supported by chronic inflammation that was initially intended to clear damaged/cancerous cells. By understanding how these immune cells are recruited and activated in solid tumors, the lab hopes to find new treatments for cancer.
As a central mediator of inflammation in tissues, activation of the complement pathway is critical for clearance of "damaged" cells, in addition to recruiting and activating immune cells to "damaged" tissues. Thus, the focus of his research is to determine whether activation of this pathway also regulates chronic inflammation associated with solid tumor development. To address this hypothesis, he is using a human papilloma vius (HPV)-mediated mouse model of cancer that effectively models cervical cancer, some head and neck cancers, skin cancer, and cancers of the anogenital region (anal, penile, vulva) in humans.
The goals of Dr. Medler's research project titled "Complement C5a Regulates Squamous Carcinogenesis" are to determine to what extent activation of the complement pathway contributes to cancer, how complement is activated in these cancers, and whether therapeutics targeting this pathway might extend to an enhanced response to current standard-of-care chemotherapy.
Tiffani A. Jones, PhDTiffani A. Jones, PhD received both a B.S. in Biology and a PhD in Genetics from the University of Utah. As an undergraduate, she investigated the mechanisms of cellular entry used by Uropathogenic E. coli. In graduate school she used the genetic model system of the fruit fly to study mechanisms of cellular morphogenesis, a process known to precede metastasis in cancer development. As a postdoctoral scientist Dr. Jones combined her background in microbiology and fly genetics to study the relationship between host-associated microbes and cancer in the laboratory of Dr. Karen Guillemin at the University of Oregon. Her project dissects the virulence mechanisms of Helicobacter pylori, a bacterial pathogen that is the primary cause of stomach cancer. H. pylori promotes cancer formation through the injection of a multifunctional protein, CagA, into the stomach lining. Tiffani has modeled this process by generating transgenic flies that express CagA in their gut cells, and she has shown that this causes excessive cell proliferation in these cells.
Helicobacter pylori is a bacterial pathogen found in the stomach of over 50% of the world's population. Many individuals infected with this pathogen are asymptomatic, however 10-20% of individuals infected with H. pylori will develop ulcers, and about 1% of infected individuals will develop stomach cancer. H. pylori strains that produce CagA are associated with increased risk of cancer. Intriguingly, recent studies have shown alterations in gut microbial communities upon H. pylori infection, which could influence disease risk. Complementing these findings, Tiffani has shown that CagA expression alters gut microbes in her fruit fly model, and that these microbes in turn enhance the excessive cell proliferation seen in this model.
To complement her work with the fruit fly, Tiffani is also investigating the role of CagA expression in the gut of the model vertebrate, the zebrafish, which harbors a gut community of a similar complexity to that of humans. CagA-expressing zebrafish have already been shown to develop intestinal tumors. Tiffani's work will dissect the roles of host genetics and resident microbial communities on caner development in this model.
Tiffani's long-term goal is to understand how interactions between host genetics and environmental factors such as microbes promote cancer initiation and development. These investigations will provide valuable new insights into the microbial context of cancer formation and offer the promise of new microbial-based diagnostics and interventions to prevent the initiation or slow the progress of cancer development.
Donor AcknowledgementThe American Cancer Society gratefully acknowledges the following individuals for their generous financial support of the 2012 Great West Division Postdoctoral Research Award:
- Anonymous donor
- Kathy and Ron Brown
- Patti and Mike Crome
- Nicholas H. and Margaret H. Carlozzi Charitable Foundation
- Eastern Star Charities Foundation
- The Williston Circle of Hope Cancer Research Fund
- Mr. and Mrs. Leonard Gibb, In Memory of Louis S. Gibb
- Rob Kinas Initiave
- Gordon Klatt Relay For Life Endowment
- Pamela and John Myerhoffer