Heat shock factor 1 directly regulates transsulfuration pathway to promote prostate cancer proliferation and survival

Our laboratory is interested in understanding the molecular and genetic events underlying cancer progression and metastasis. The focus of our work is a series of genetically engineered mouse models that faithfully recapitulate human disease. Using a combination of mouse genetics, omics technologies, cross-species analyses and in vitro approaches, we aim to identify cancer cell–intrinsic and –extrinsic mechanisms driving metastatic cancer progression, with a long–term goal of developing new therapeutic strategies for preventing and treating metastatic disease. 

The overarching goal of the Macias lab is to gain basic mechanistic insights into clinically relevant actionable molecular targets with the eventual goal of aiding to reduce prostate cancer-specific mortality.

Our group integrates human cancer genomic data, functional genomic loss of function screens and pre-clinical in vitro and in vivo mouse models in order to identify, prioritize and validate potential therapeutic targets. Recently, we conducted a functional genomic kinome screen in obese and calorie restricted mice that identified various orphan kinases that are essential for tumor growth in an obese and lean host environment. We are steadily adapting drug development discovery capabilities and lead compound optimization strategies for increased target engagement, efficacy and drug like properties via collaboration with medicinal chemists and structural biologists. In parallel, we are conducting basic mechanistic studies to determine the mechanism of action, including live cell imaging phenotypic gain and loss of function genetic studies and various omic approaches.

I am a physician-scientist with clinical expertise in the pathologic diagnosis of genitourinary tumors including tumors of the prostate, bladder, kidney and testis. Another area of interest is gynecologic tumors. In my research laboratory we study prostate cancer, focusing on molecular mechanisms of carcinogenesis and tumor progression, as well as biomarkers, imaging and novel therapeutic strategies. In addition to patient care and research, I am also passionate about education. I have trained numerous residents, fellows, graduate students and postdocs.