Larry Mylin's Research
Professor of Biology
I am interested in how the cellular immune system can control cancer. The immune system should be able to use fragments of foreign or abnormal proteins (antigens) expressed by altered cells as a means to detect and destroy them. We wish to gain a better understanding of factors that control recognition of tumor cell antigens by CD8+ cytotoxic T lymphocytes (CTL), and how CD4+ T helper T cells stimulated by other parts of the same antigen(s) can regulate the production and longevity of the tumor-specific CD8+ T cells. Multiple factors control whether or not immunization with a complex antigen results in the efficient recruitment and expansion of CD8+ T cells specifically focused at discrete parts of the antigen protein.
We study two model cancer targets in murine immunogenetic systems: the Simian virus 40 large tumor antigen (SV40 T ag) and a splice variant of the human cholecystokinin receptor. The SV 40 T ag can convert normal mouse cells into cancerous cells. However, the presence of the T ag in the cancer cells provides targets (epitopes) that allow for their recognition and destruction by CD8+ T lymphocytes of the host immune system. Multiple projects have investigated factors that control the immunogenic potential of the multiple epitopes found within the SV40 T ag protein. We are currently studying the role of CD4+ T lymphocytes induced by multiple additional epitopes in the T ag protein. Other projects have examined how readily these epitope targets can mutate to allow T ag-transformed tumor cells to escape destruction by otherwise potent CTL. We have just begun to map epitopes in the CCKC receptor, and are testing their ability to control the growth of murine tumors engineered to express the cancer-associated form of the CCKCR. These research projects are conducted primarily by my undergraduate student researchers.
My laboratory also seeks to support malaria research that is conducted in Zambia (Africa) by scientists working at the Macha Research Trust. The Macha Research Trust (formerly Malaria Institute at Macha, MIAM) was established in 2005 in collaboration with The Johns Hopkins Bloomberg School of Public Health Malaria Research Institute by a Messiah University alum who had served as a pediatrician and malaria researcher at the neighboring Macha Mission Hospital for two decades. I spent a spring semester sabbatical in Macha developing appropriate technology and culture methods, and training the local scientists to allow research employing malaria culture to be conducted on site in rural southern Zambia.
Finding ongoing, adequate supply of fresh human blood form uninfected donors remains and ongoing limitation for malaria culture studies at Macha. Accordingly, we have begun to study how to revise our culture methods so that human blood can be collected from uninfected donors in the US, frozen, and used later for culture studies in Zambia. Our initial studies indicate that blood frozen under defined conditions does support propagation of P. falciparum even after storage at -80°C for more than a year.
Finally, I am always thinking of new ways to allow students to learn in hands-on ways in traditional course laboratory sessions. I have developed multiple laboratory exercises that are now used in my courses. Research students routinely collaborate with me to develop the new modules and reagents.