Vincent Sollars, PhD
Director of the Flow Cytometry Core, Associate Professor
Phone: (304) 696-7357
sollars@marshall.edu

Research Experience

What mechanisms assist an initiated premalignant cell in progression to a fully transformed state? The answer to this key question will help us to understand why our bodies are successful in the eradication of some premalignant masses, while unsuccessful in others. Such understanding will be instrumental in designing chemotherapeutic strategies that target aspects of cancer not related to proliferation and allow for eradication and control of cancer stem cells. Since Dr. Feinberg’s initial investigations into epigenetic gene regulation and cancer it has become increasingly apparent that epigenetic gene regulation is an important aspect of cancer progression. However, as he pointed out in a review, epigenetics is not simply another layer of gene control but a potential mechanism of control of cellular variability. Thus, alteration of epigenetics can go beyond the realm of silencing of tumor suppressors and activation of oncogenes and contribute to increased heterogeneity or cellular plasticity of the tumor mass. This mechanism could be a powerful and as yet poorly described means of tumor progression and consequently a high value target for cancer therapeutics.

As many cancers evolve they acquire an addiction to Heat Shock Protein 90 (HSP90) as a result of the stochastic mutational process they rely upon for that evolution. The random nature of mutation makes it necessary that any mutation a pre-malignant cell acquires that is beneficial must be accompanied by a host of other mutations that can have deleterious effects. The addiction that cancers develop to HSP90 originates from this relationship. HSP90 has chaperonin capabilities that allow the cell to overcome problems with protein aggregation, protein misfolding, and cellular stress that are a result of deleterious changes in proteins. This is an exciting concept in chemotherapy because it offers a molecular mechanism as a target that does not rely upon the defining attribute of cancers, uncontrolled cellular proliferation, that almost all chemotherapies target. This realization has prompted a host of research efforts aimed at intelligently designed inhibitors based mainly upon geldanamycin derived inhibitors to HSP90. Unfortunately, clinical trials using these inhibitors have had lackluster success. To realize the vast potential of HSP90 as a chemotherapeutic target we must more fully understand the relationship between HSP90 and the evolution of cancers.

Impaired differentiation is a hallmark of many forms of cancer, but particularly pronounced in myeloid leukemias. The objective of my research is to identify new chemotherapeutic approaches for the treatment of myelogenous leukemia by focusing on elucidating the mechanisms of epigenetic gene regulation of myeloid cellular variation during differentiation. Epigenetic gene regulation is of preeminent importance in the control of cell identity during differentiation and is at the forefront of research in chemotherapy. The murine model system is the premiere model for studying human disease. My laboratory is using this model system to study epigenetic gene regulation of myeloid cell differentiation in the bone marrow. We are primarily interested in the role of HSP90 in controlling variation in phenotypic plasticity at the epigenetic level and its role in modulating signal transduction pathways. We are also interested in how diet and other microenvironmental cues are processed into epigenetic information and influence phenotypic variation and cancer susceptibility. We primarily use a murine cell culture system of hematopoietic stem cells to study these processes. We are also using mice in mapping studies to identify genes important in these control mechanisms, determining the nature of the regulatory mechanisms, and in testing hypotheses concerning epigenetic gene regulation.