The goal of my research is to understand the mechanistic underpinnings of the cell signaling networks that contribute to cancer progression and resistance to therapy. My laboratory is currently focused on 1) testing the hypothesis that HULLK, the novel lncRNA we discovered, functions as an oncogene and a clinical biomarker in prostate cancer (PCa); 2) studying how heterotypic cell signaling in the tumor microenvironment determines sensitivity to immune checkpoint inhibitors; and 3) looking for combinatorial therapeutic targets in PCa.

Current Projects

  • HULLK mechanism. We have recently published the discovery of a novel lncRNA that acts as an oncogene in PCa that we have named “HULLK” for Hormone-Upregulated lncRNA within LCK (PMID:31253147). shRNAs specifically targeting HULLK significantly decreased PCa cell growth whereas overexpression of HULLK enhanced PCa cell growth. We are currently testing the hypothesis that HULLK is a novel lncRNA that functions as a targetable oncogene in PCa. Funded by NCI.
  • HULLK biomarker. HULLK transcripts are expressed in androgen receptor (AR) positive PCa cell lines and in patient tissue. There is a significant positive correlation between HULLK expression and high-grade PCa in three independent cohorts: the University of Virginia, the University of Texas Southwestern, and The Cancer Genome Atlas (PMID:31253147). We are currently testing the hypothesis that HULLK is a biomarker for PCa. We have established that we can detect HULLK in the urine of a subset of men with high grade PCa. Funded by APIS Assay Technologies.
  • PCa therapy. Our unpublished data show that inhibition of the CBFb-RUNX interaction synergizes with the AR antagonist, enzalutamide, and with siRNA targeting AR to effectively inhibit PCa tumor cell growth. We are testing the hypothesis that co-targeting the transcription factors CBFb-RUNX and AR using a novel nanopharmaceutical, P-TRIS5, could be an effective treatment strategy. P-TRIS5 is a functionalized DNA nano-carrier with 1) a binding peptide specific to PSMA (prostate-specific membrane antigen) for targeted delivery; 2) the dTAT peptide for endosomal release; 3) a CBFb-RUNX inhibitor (14-91); and 4) an siRNA to the AR that targets both full-length and AR splice variants known to drive PCa. Funded by NCI.
  • AR function in PCa. My lab uncovered novel molecular interactions between the DNA Damage Response (DDR) effector CHK2 and the AR that provide mechanistic insight into how CHK2 negatively regulates prostate cancer growth (PMID:32579110; PMID:26573794). This led my lab to use Precision Run-On Sequencing (PRO-Seq), a novel technique that enables quantification of nascent RNA transcripts, to identify AR dependent DDR genes. We discovered that, contrary to dogma, enzalutamide treatment did not globally affect the IR-induced DDR changes in gene expression patterns.
  • TMES. We have developed a human Tumor Microenvironment System (TMES) that exposes primary human cells to tumor hemodynamics and transport that recapitulates in vivo-like biology (PMID:30839006; PMID:33692370). We have validated TMES builds for pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and proof-of-concept for PCa. In PDAC, there are conflicting results between preclinical experiments and clinical trials targeting the stroma; a more predictive experimental system that reflects PDAC patient biology is critically needed. We are proposing to use the TMES to address this need through the expansion of the PDAC TMES to incorporate the diversity of stromal cells and immune cells. This improved TMES will be used to conduct mechanistic studies on how the tumor microenvironment impacts therapeutic response. We have also recently used the TMES to study how NSCLC tumor cells that harbor KRAS and EGFR mutations alter tumor endothelial cells (TECs). Our data has led us to the hypothesis that cancer cells induce changes in the expression of immune modulatory proteins in TECs in an oncogene dependent manner; this, in turn, determines the efficacy of immune checkpoint inhibitors in NSCLC. This discovery could explain why NCSCL patients with EGFR mutations typically have a poor response to immunotherapy where KRAS mutation NSCLC patients show consistent benefit to immunotherapy.


Together, each of the initiatives described above contribute to the central goal of my research program, which is to understand how crosstalk among signal transduction pathways contributes to cancer progression in complex models of disease, and how that information can be used to develop more effective cancer treatments.