Alyssa R. Summers
Associate Professor of Biology, Co-Chair of Biochemistry & Director of Office of Medical and Health Programs and Summer STEM Bridge Program
B.A., Lawrence University; Ph.D., Vanderbilt University
Interests and Topics of Study: Molecular Cell Biology, Molecular Genetics, Epigenetics, Cancer Cell Biology, and Medical Humanities
My interest and responsibilities at Sewanee are diverse. I enjoy teaching topics that explore the complexity of DNA and the implications of genetic differences in cellular development and disease. In addition to the sciences, I am interesting in gaining insight into the work done to understand how we percieve our own humanity, in particular how this realization may allow us to become better healers and practitioners of medical care, thus I have recently been exploring topics within the expansive discipline of medical humanities.
My research focuses broadly on understanding how our DNA is organized and accessed. Through understanding these basic science questions we can learn about how cells develop and what goes wrong during disease states that might help to create novel treatments. In more technical terms, I focus on understanding how transcriptional networks regulate cell fates, tissue development, and cancer. In particular, my lab group studies how a chromatin modifying enzyme, called Hdac3, can regulate gene expression patterns that impact cell function. To do this we use several mouse model systems that knock-out Hdac3 in specific tissues. I am passionate about giving undergraduate students research experiences and welcome student scientists who are curious, hard working, have great initiative, and understand that science is a time commitment. Equally important to me is creating opportunities for students to not only engage in the hands-on lab experiences, but also the practical aspect of science communication. Thus, it is an expectation in my lab that all students will present their work at Scholarship Sewanee. Additionally, I along with Dr. Elise Kikis, created the Journal of Sewanee Science (JoSS) to engage students in written science communication; please see the JoSS website for new article submissions and past journal content.
In additional to my academic interests, I have several administrative responsibilities. I am the Director of two programs, Pre-health and Bridge, that aim to help students achieve their goals in medicine and science, serve as Co-Chair of the interdisciplinary Biochemistry Program (with Dr. Bethel Seballos), and am a member of the Neuroscience Steering Committee. The Bridge program is for rising senior high school students interested STEM disiplines; more information can be found at the Summer STEM Bridge Program website. As the Director of the Office of Medical and Health Programs (OMHP) I work with all students who might have an interest in healthcare; from medicine focused on helping people or animals to nursing, physical therapy, physician assistant, pharmacy, nutritionist, or public health. For more information about the pre-health program visit our website and/or facebook page.
Sewanee has an inviting and expansive pre-health program that aims to serve all pre-health disciplines. As the Director of the Office of Medical and Health Programs (OMHP) I am available to answer questions regarding pre-medical and pre-health education and opportunities. Additionally, OMHP partners with Career and Leadership (CLD), liaison Lisa Howick, who can help find internships, alumni connections, and help with personal statements and interviews skills. Pre-medical students needing guidance about committee letters for medical school applications, should contact the Chair of the Pre-Health Advisory Committee, Dr. Rich Summers. Additional information can be found on the website with up to date information about curriculum, internships (like the V-SURE program shown above during summer of 2015), tutoring, student groups and societies, as well as other program opportunities.
STUDENT RESEARCH OPPORTUNITIES
Breast cancer is a complex disease that arises from both genetic and epigenetic alterations. Currently treatments involving histone deacetylase inhibitors (HDI) have emerged as viable treatment options, particularly when combined with other systemic therapies. We aim to more fully elucidate the specific role that HDACs play in regulating breast cancer cell function during tumor progression. Using a conditional knock-out mouse model we have removed Hdac3 from the mammary gland and induced tumorigenesis using the viral gene polyoma middle T-antigen. Additionally, we use various pan-HDIs (such as SAHA and Depsipeptide) and a specific Hdac 3 inhibitor to evaluate cell motility, proliferation and death in a panel of breast cancer cell lines.
1.Mammary Gland Development: This project aims to determine the biological role of Hdac3 in mammary gland development from birth through lactation and involution. Due to the use of HDIs in the treatment of cancer, as well as neurological disorders, it is imperative to understand the biological role of Hdac3 on normal cell function.
2.Breast Cancer Initiation and Progression: This project utilizes a mouse model and cell culture to examine the role that Hdac3 plays in tumor formation and progression.
T-CELL DEVELOPMENT PROJECT
Histone Deacetylase Complex 3 (Hdac3) is an epigenetic modifier that negatively regulates gene expression through the removal of acetyl groups from histone proteins. Due to the lethality of a total knock-out of this protein, we constructed a conditional knock-out mouse model that selectively removes Hdac3 in the thymus. Previous analysis in our lab showed that Hdac3 knock-out at an early stage of thymocyte development greatly reduced the number of functional peripheral T-cells. The majority of thymocytes became blocked in the immature Double Positive (DP) stage of development with limited expression of TCR, suggesting a crucial role for Hdac3 in T-cell maturation and function. Further analysis using Microarrays suggested a role for GIMAP proteins in this process, as 4 GIMAP genes were differentially expressed in the Hdac3 null thymoctyes. We are continuing to analyze the role of Hdac3 in T-cell development by examining GIMAPs and VDJ recombination of TCR alpha and beta genes.
1.T-cell regulation by GIMAP proteins: This projects focuses of the development and function of T-cells. GIMAPs were identified as potential genes regulated by Hdac3. We aim to determine the transcriptional role that Hdac3 plays in GIMAP expression and their functional consequences.
2.T-cell VDJ rearrangement and chromatin remodeling impact on TCR repertoire diversity: This project involves examining the function of Hdac3 in chromatin remodeling and how this impacts VDJ recombination and TCR (T-cell Receptor) expression. Efficient VDJ recombination impacts TCR diversity. The more diverse range of TCRs expressed on T-cells the better off we are at fighting off new pathogens, thus we aim to elucidate the role of Hdac3 in immune function.
Class of 2012: Mary Emily Christensen, Logan Miller, and Laura Bownes
Class of 2013: Carmen Rinio and Taylor Stavely
Class of 2014: Nick Klus and Sarah Brown
Class of 2015: Sydney Philpott, Andy Streiff, Angelica DeFreitas, and Jordan Buck
Class of 2016: Amiel Emerson, Jacob Zalewski, Sarah Christie, and David Pride
Class of 2017: Sara Jayne Sutton
Class of 2018: Elizabeth Gill, ZsanettPeter, and Emily Shriner
Class of 2019: Meredith Sackett
STUDENT MENTORED PUBLICATIONS and PRESENTATIONS
Zalewski J. Luciferase Reporter Assay Technology: A modern approach to studying gene expression and promoter element activity. (2015) JoSS V1(1):5-6.
Pride D. ChIP-seq: The new gold standard in the study of protein-DNA interaction. (2015) JoSS V1(1):7-9.
DeFreitas A. Role of histone deacetylase in mammary tumorigenesis. (2015)Honors Thesis in Biology.
Brown S, DeFreitas A, and Philpott S. Anti-tumorigenic properties of HDAC inhibition on mammary tumorigenesis. (2015) Scholarship Sewanee, prize recipient 3rd place in Biological Sciences
Christie S. and Pride D. Transcriptional regulation of GIMAP proteins. (2015) Scholarship Sewanee
Buck J, Emerson A, and Zalewski J. HDAC3-mediated transcriptional control of GIMAP genes. (2015) Scholarship Sewnaee
Brown S, DeFreitas A, Philpott S. Effects of HDACs in advanced stage breast cancer signaling and cell function. (2014) Scholarship Sewanee, prize recipient 2nd place in Biological Sciences
Klus NJ. Role of HDACs in GIMAP transcriptional regulation and function in T-cell development. (2014) National Undergraduate Research Conference (NCUR)
PUBLICATIONS and CONFERENCE PRESENTATIONS
Stengel KR, Zhao Y, Klus NJ, Kaiser JF, Gordy LE, Joyce S, Hiebert SW, Summers AR. Histone Deacetylase 3 is required for efficient T-cell development. Molecular Cell Biology (2015) V35: 3854-3865.
Brown S, DeFreitas A, Philpott S, Summers AR. The role of Hdac3 in breast cancer cell function. (2014) Keystone Conference: Cancer Epigenetics
Summers AR, Fischer MA, Stengel KR, Zhao Y, Kaiser JF, Wells CE, Hunt A, Bhaskara S, Luzwick JW, Sampathi S, Chen X, Thompson MA, Cortez D, Hiebert SW. Hdac3 is essential for DNA replication in hematopoietic cells. Journal of Clinic Investigation (2013) V123 (7): 3112-23.
Klus N, Kaiser JF, Hiebert SW, Summers AR. Hdac3 is required for efficient selection of double positive thymocytes during T-cell development (2012) Keystone Conference: Chromatin Dynamics and Epigenetic Mechanisms
Bhaskara S, Knutson SK, Jiang G, Chandrasekharan MB, Wilson AJ, Zheng s, Yenamandra A, Locke K, Yuan J, Summers AR, Washington K, Zhou Z, Sun Z, Xia F, Khabele D, Hiebert SW. Hdac3 is essential for maintenance of chromatin structure and genome stability. Cancer Cell (2010) V18(5): 436-447.
Summers AR, Brown KA, Aakre ME, Arteaga C, Pietenpol JA, Moses HL, Cheng N. Epidermal Growth Factor Receptor plays a significant role in mediating Hepatocyte Growth Factor biological responses in mammary epithelial cells. Cancer Biology and Therapy (2007) V6(4): 561-570.
Summers AR, Law BL, Moses HL. Chapter: Transforming Growth Factor ß and Cancer, Cytokines in the Genesis and Treatment of Cancer. Edited by M. Caligiuri and M. Lotze. New Jersey: Humana Press Inc, 2007.
Areas of ExpertiseMolecular Cell Biology, Molecular Genetics, Epigenetics, and Cancer Cell Biology