Elliott Associate Professor of Biology Dr. Kristian M. Hargadon recently contributed a comprehensive review article on dendritic-cell based immunotherapy for melanoma to a special issue of Frontiers in Immunology. An expert in tumor immunology who has conducted cutting-edge research on melanoma-associated suppression of dendritic cell function, Dr. Hargadon was invited in the summer of 2017 to contribute to the Frontiers in Immunology Research Topic “New Therapies and Immunological Findings in Melanoma and Other Skin Cancers,” a special issue for the journal edited by Dr. Atsushi Otsuka of Kyoto University in Japan and Dr. Reinhard Dummer of University Hospital Zurich in Switzerland. Dr. Hargadon’s article discusses not only the most current research on dendritic cell immunosuppression by melanoma but also other factors that influence dendritic cell function in the context of this cancer, including factors that influence the immunogenicity of tumor cell death, tumor-altered dendritic cell metabolism, and microbiome influences on dendritic cell-mediated anti-tumor immunity. His article highlights the current state of dendritic cell immunotherapy for melanoma and discusses future challenges that will need to be overcome to further improve the efficacy of dendritic cell-based therapies for this cancer.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies. It is the leading and most-cited Open Access journal in the field of Immunology and is the 5th most cited overall of 150 journals in the field of Immunology. Dr. Hargadon’s article can be accessed at https://www.frontiersin.org/articles/10.3389/fimmu.2017.01594/full
On Saturday Sept. 23 Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01 joined more than 300 cancer researchers from major research universities across the state to present recent work from his laboratory at the inaugural Commonwealth of Virginia Cancer Research Conference held at the University of Virginia. Dr. Hargadon’s presentation focused on the role of the FOXC2 transcription factor as a critical driver of melanoma progression and featured work that he has conducted with 6 Hampden-Sydney College students over the last two years, all of whom were co-authors on the presentation. These student co-authors include Jefferson Thompson ’16 (applying to medical school), Travis Goodloe ’16 (now at University of South Alabama School of Medicine), James Lau ’17 (now at Eastern Virginia Medical School), Corey Williams ’19 (already accepted at Virginia Commonwealth University School of Medicine), Coleman Johnson ’19 (already accepted at Virginia Commonwealth University School of Medicine), and David Bushhouse ’19 (plans to pursue Ph.D. in a field of molecular genetics). Both Corey Williams ’19 and David Bushhouse ’19 joined Dr. Hargadon at the symposium and experienced firsthand the enthusiasm and momentum currently running through the field of cancer research. Major themes of the conference included new insights into molecular drivers of cancer progression and strategies to improve on the already promising targeted and immune-based therapies that are revolutionizing cancer treatment.
Dr. Kristian M. Hargadon ’01 presenting his work on the role of FOXC2 in promoting lymph node metastasis by melanoma.
This summer, 3 rising H-SC juniors have been conducting melanoma research with Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01. David Bushhouse, Coleman Johnson, and Corey Williams are investigating the role of the FOXC2 transcription factor as a driver of melanoma progression. Specifically, Corey has performed extensive phenotypic analyses of various wild-type and genetically engineered melanoma cells to study how FOXC2 expression in melanoma influences the expression of various integrins and other cell adhesion molecules on tumor cells. In related work, Cole has focused on studying how FOXC2 expression within these melanoma cells influences tumor cell adhesion to both the extracellular matrix and lymphatic endothelial cells, processes that are instrumental in determining whether or not a tumor is able to metastasize to distant sites in the body. In conjunction with this work, David is performing chromatin immunoprecipition studies to determine whether the regulation of cell adhesion molecule gene expression in melanoma cells that is driven by FOXC2 results from a direct interaction between this transcription factor and specific gene segments within the DNA of melanoma cells. Collectively, this work is shaping our understanding of FOXC2’s role in melanoma progression and has the potential to identify several potential targets for cancer therapies designed to interfere with the progression of this cancer. Cole and Corey were recently accepted into the Virginia Commonwealth University School of Medicine Early Selection Program, and David is planning to pursue a Ph.D. in the biomedical sciences.
Corey Williams ’19 preparing melanoma cells for flow cytometric analysis of integrin expression!
Cole Johnson ’19 setting up a tumor cell/extracellular matrix adhesion assay!
David Bushhouse ’19 isolating chromatin from melanoma cells to assess target genes of the FOXC2 transcription factor!
On December 5, the H-SC Biology Department had a special visitor lurking the halls, The Grinch! During this time, one Professor Hargadon was nowhere to be found, and upon the Grinch’s visit to a Microbiology class, students feared that their Christmas dreams of good grades would be stolen away. However, they soon realized that, as the story goes, the Grinch’s heart grew 3 sizes at Christmas, and many students were even given the gift of a final exam exemption!
The Grinch with his trusty companion, Max (aka Trickie)!
Conspicuous by his absence, Dr. Hargadon could not even be found in his usual spot (the laminar flow hood) during the Grinch’s visit. Rest assured, though, the Grinch saved the day and continued his work. Melanoma doesn’t stand a chance!
The Grinch hard at work in Gilmer Hall!
Senior Biology major James Lau ’17 recently received the Best Poster Award for a poster presentation of his research at the 4th
Annual Longwood University/Hampden-Sydney College Sigma Xi Research Symposium. The symposium featured a talk by keynote speaker Dr. Steve Cresawn of James Madison University and was highlighted by a student poster presentation featuring 22 undergraduate researchers from both Longwood University and Hampden-Sydney College. James, who was recently named only the 3rd
Goldwater Scholar in the history of H-SC, presented research he has been conducting in collaboration with Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01. James began working in Dr. Hargadon’s laboratory in the summer of 2016 on a project designed to investigate the role of the Foxc2
gene in regulating the progression of melanoma, the most aggressive form of skin cancer. James is continuing his research with Dr. Hargadon throughout his senior year for his Departmental Honors project, which is focused on assessing how expression of the FOXC2 transcription factor regulates tumor migration and invasion within tissues, key processes that ultimately contribute to tumor metastasis. Following his graduation, James will be attending medical school at Eastern Virginia Medical School, where he was accepted as a sophomore through the College’s Early Admission Program with EVMS!
Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01 recently published a major review article on the role of TGFb1 in compromising the quality of anti-tumor immune responses. Following a recent publication by Dr. Hargadon and collaborating Hampden-Sydney College students in the journal Immunology and Cell Biology, which described TGFb1’s alteration of dendritic cell function in melanoma, Dr. Hargadon was invited by editors of the Journal of Clinical Medicine to submit a comprehensive review article on TGFbeta1’s influence on the anti-tumor immune responses. Dr. Hargadon’s article, entitled “Dysregulation of TGF1 Activity in Cancer and Its Influence on the Quality of Anti-Tumor Immunity” appears in the Journal of Clinical Medicine’s Special Issue dedicated to the topic “Biological and Clinical Aspects of TGF-beta in Carcinogenesis.” Dr. Hargadon’s article highlights current understanding in the field of tumor-associated TGFb1’s ability to compromise the function of several immune cell populations, including dendritic cells, T cells, macrophages, and neutrophils, and it highlights how our knowledge of TGFb1’s immunosuppressive mechanisms is being translated into novel immune therapies in the clinical setting. This article can be found at the following link: http://www.mdpi.com/2077-0383/5/9/76
Ongoing research in Dr. Hargadon’s laboratory at Hampden-Sydney College is focused on understanding immune suppression by melanoma and elucidating the function of genes that promote melanoma progression. Since returning to his alma mater in 2009, Dr. Hargadon has involved 12 Hampden-Sydney College students in independent research projects related to this work, and he has incorporated aspects of his research into his Biology 201 Genetics and Cell Biology course, where 15-20 students are involved in melanoma research each year that he offers the course.
This summer two Hampden-Sydney College Biology majors, James Lau ’17 and Brant Boucher ’17, are conducting melanoma research alongside Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01. Previous research in the Hargadon laboratory has shown a role for the FOXC2 transcription factor in promoting melanoma growth and metastasis, and James and Brant are currently investigating different aspects of FOXC2 as it relates to melanoma progression. Using a mouse melanoma model, James is comparing gene and protein expression profiles of a highly aggressive melanoma cell line that expresses high levels of FOXC2 versus a CRISPR-Cas9 gene-edited version of this melanoma in which the Foxc2
gene has been disrupted. This work will provide insights into genes that may be positively or negatively regulated by FOXC2 and will improve our understanding of how FOXC2 promotes aggressive behavior in cancer cells. In related work, Brant is investigating a novel gene silencing approach that aims to shut down Foxc2
gene expression specifically in melanoma cells. The ability to turn this gene off specifically in melanoma cells would offer an exciting opportunity to prevent the tumor-promoting functions of this gene in cancer cells without impacting FOXC2’s normal function in healthy cells. Both James and Brant have already been accepted to medical school and will begin following their graduation from H-SC in 2017!
James Lau ’17 performing flow cytometric analysis of B16-F1 melanoma cells containing functional versus disrupted Foxc2 genes.
Brant Boucher ’17 setting up a real-time PCR reaction to assess melanoma-specific silencing of the Foxc2 gene.
Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01 was recently invited to become a member of the European Academy of Tumor Immunology by the Academy’s Governing Body. Founded in 2011 to promote tumor immunology at the scientific and clinical levels, the European Academy of Tumor Immunology (EATI) aims to “bridge fields, bridge continents, and bridge generations” of tumor immunologists across the globe who are studying tumor immunity at fundamental, translational, and clinical levels. With his membership in EATI, Dr. Hargadon, whose research at Hampden-Sydney College focuses on immune suppression by melanoma, joins an international group of 360 tumor immunologists that includes 3 Nobel Laureates and many of the leading cancer researchers in the world.
Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01 was recently awarded a $100,000 grant from the Jeffress Trusts Awards Program in Interdisciplinary Research to support his melanoma research program. Funds from this grant will be used by Dr. Hargadon and his collaborating Hampden-Sydney College students to investigate anti-tumor CD8+ T cell dysfunction and the ways in which lymph node invasion by melanoma impacts the quality of tumor-specific CD8+ T cell immune responses. Understanding these processes will shed light on mechanisms by which tumors evade immune destruction, and this knowledge may ultimately inform the design of novel immunotherapies that aim to improve the quality of anti-tumor immunity.
On March 30, ten Hampden-Sydney College students were inducted into Sigma Xi, the international honorary scientific research society. Founded in 1886 to honor excellence in scientific investigation and to encourage collaboration among researchers in all fields of science and engineering, the Society now consists of over 500 chapters at academic, industrial, and government research institutions and has nearly 60,000 members in more than 100 countries around the world. The Longwood University/Hampden-Sydney College chapter of Sigma Xi was reactivated in 2013, and the two institutions now alternate hosting an annual Sigma Xi Research Symposium that features a keynote speaker and student poster presentations highlighting recent research activities on both campuses. Congratulations to the H-SC students inducted in 2016: Branch Vincent, Christopher Hawk, J.D. Chaudhry, Jefferson Thompson, Linh Nguyen, Mitchell Thomas, Shaquann Seadrow, Will Echols, Will Fitzgerald, and Zachary Martin.