Identification of a Germline Pyrin Variant in a Metastatic Melanoma Patient With Multiple Spontaneous Regressions and Immune-related Adverse Events.

I am dermatopathologist with special interest in melanocytic pathology (including molecular alterations and tests that aid in predicting their biologic behavior), and soft tissue pathology

I am an Assistant Professor of Medical Oncology who primarily treats patients with colon cancer and gastroesophageal cancers. My laboratory and translational research is focused on tumor immune evasion and immunotherapy, particularly in the setting of metastasis. This work has led to a specific interest in tumor-mediated development of dendritic cell tolerance and suppressive myeloid populations. The ultimate goal of this research is to create biomarker-directed immunotherapies for advanced gastrointestinal cancers.

Using Pathogens to Decipher Genetic Variation Connecting Cell Biology and Disease Susceptibility
Despite improvements in public health, advancements in vaccines, and the development of many classes of antibiotics, infectious disease is still responsible for over a quarter of all deaths worldwide. However, even for the most devastating of pandemics, individuals demonstrate a large variability in the severity of infection. The long-term goal of the lab is to understand the genetic basis for differences in susceptibility to infection and related inflammatory disorders. We approach this question through a combination of experimental and computational approaches that combine high-throughput cell biology with quantitative human genetics. The identified genetic differences serve as the starting point for exploring new cell biology and human disease susceptibility genes.

We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these agents. We strive to translate our understanding of the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance into early phase clinical trial testing.

Our work utilizes a variety of techniques and methodologies that span the breadth of basic biological research. This work integrates studies based on both 1) transgenic mouse tumor models that are monitored using bioluminescence and micro-CT imaging and 2) a variety of clinical specimens.

Our current areas of focus include:

1. Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
2. Studying the relationship between EMT pathways and immunotherapy resistance.
3. Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
4. Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
5. Investigating mechanisms contributing to select immunotherapy-associated toxicities