T-Cell Lymphomas (TCL) are a heterogeneous group of highly aggressive mature non-Hodgkin lymphomas that has its genesis from the malignant transformation of mature T-cells. Unfortunately, TCLs are generally associated with poor prognosis and most of the current therapies show limited efficacy and none are curative, making relapsed/resistant TCL a major clinical problem. One promising line of therapy currently being explored in the field involves the use of an epigenetic class of therapeutics, histone deacetylase inhibitors (HDACi). However, many patients will not respond to HDACi treatment and among those that do, resistance is inevitable. Using a well-defined bank of T-cell lymphoma patient samples undergoing HDACi therapy, I aim to identify the underlying genetic aberrations that lead to HDACi resistance. Through these results, I hope to improve out understanding of TCL pathogenesis during HDACi treatment and to develop novel strategies to overcome resistance.
Using high throughput techniques in a variety of T-cell lymphoma cell lines, I have identified a number of compounds that are potentially synergistic with HDACis. These hits are currently being validated in TCL cell lines, with the goal of testing validated hits in vivo.
The study of T-cell lymphomas has been complicated not only by relative rareity of the malignancy but also the highly heterogeneous nature of this class of malignancy. Further complicating the study of T-cell lymphomas is the uncharacterized role of the tumor-microenvironment that may work in concert with tumor cell epigenetic and genetic aberrations. To this end, we have identified a large and well-annotated group of frozen Angioimmunoblastic T-Cell Lymphomas as well as Peripheral T-Cell Lymphoma Not-Otherwise-Specified patient samples biopsied from either the lymph node or tonsil along with healthy controls at Columbia University Medical Center. We aim to use single-cell technologies to deconvolute tumor heterogeneity, identify genetic/epigenetic drivers of lymphomagenesis within the tumor cell, and profile tumor-microenvironment interactions that may play a role in immune evasion or tumor activation. These findings will be validated using several in vitro and in vivo models that have been developed in our lab.
For examples of my computational analysis, please look on my Github. Many of the analyses I have performed are not public, but I would be more than happy to discuss my work privately, so don't hesitate to reach out!
