J. Joshua Smith

I am a surgeon-scientist, Associate Member and board-certified attending surgeon on the Colorectal Service at Memorial Sloan Kettering Cancer Center (MSK). My clinical practice is directly reflected in my ongoing basic and translational colorectal cancer research efforts. In the clinic, my efforts are directed entirely toward the treatment of patients with rectal, colon and anal cancer. In the lab, I work to understand the molecular underpinnings of disease progression and to develop individualized disease models that will facilitate both effective research and precision treatment. I completed my general surgery training at Vanderbilt University Medical Center. I also completed a PhD in cell and developmental biology at Vanderbilt University in the midst of my residency. My doctoral research, conducted in Dan Beauchamp's laboratory, used comparative functional genomics and models of cancer biology to investigate the mechanisms by which colorectal cancer cells become metastatic. I then completed a fellowship in surgical oncology with an emphasis in colon and rectal cancer under the guidance of Dr. Julio Garcia-Aguilar at MSK. I also served as Chief Administrative Fellow for the Department of Surgery at Memorial Hospital from 2014 to 2015. The majority of my time is devoted to NCI-funded basic and translational research. I can leverage the strengths of MSK, including the high volume of rectal cancer patients treated by our group (>350/year) and the opportunity to run clinical trials. For example, I have been active in the recently completed randomized trial integrating non-operative management for selected patients with rectal cancer (NCT02008656 - PMID 35483010) with my clinical mentor Dr. Garcia-Aguilar. In collaboration with investigators at the Alliance for Clinical Trials, NRG Oncology and SWOG, we have now expanded these findings to a national phase II trial. I am the PI of this Alliance for Clinical Trials-led, NCTN-wide randomized Phase II Janus Rectal Cancer Trial, sponsored by the NCI (NCT05610163). The Janus Rectal Cancer Trial is testing the addition of irinotecan to standard FOLFOX after long-course chemoradiation for locally advanced rectal cancer patients to improve the rate of complete response and long-term organ preservation. My chief objective as a clinician and scientist is to uncover more precise treatments for each individual rectal cancer patient. To discover potential therapeutic targets and prognostic markers, I apply functional genomics to patients' tumor samples. To develop the means to assess treatment options for the individual patient in co-clinical trials, I investigate methods to model individual rectal tumors in vitro and in vivo. I have already developed, in collaboration with Scott Lowe and Charles Sawyers, the first relevant rectal cancer model, which involves endoluminal implantation of human rectal tumors into mice (PMID 31591597). We have subsequently developed a functional immunocompetent rectal cancer model in which radiotherapy approaches and mechanisms can be tested (PMID 36590695). We are now moving toward translating basic and translational findings to the clinical realm with co-clinical trials, whilst developing the next generation of clinical trial platforms aimed at improving outcomes for our patients.