Memorial Hospital Research Laboratories
The J. Joshua Smith Lab
The J. Joshua Smith Laboratory focuses on making better models of rectal cancer (RC). My laboratory group developed the first patient-derived rectal cancer organoids. These rectal cancer organoids recapitulate the clinical and molecular features of patients with rectal cancer and uniquely reflect the clinical responses to therapy of the patients from which they were derived. I obtained an R37 grant from the National Institutes of Health to further develop and expand this rectal cancer model, and my work as a clinician and clinical trialist completely overlaps with my basic and translational work. Our focus is on improving response to neoadjuvant therapies for patients with rectal cancer by developing better disease models. I have a strong collaborative relationship with surgeon Julio Garcia-Aguilar, Chief of the Colorectal Service; radiation oncologist Paul Romesser; and surgeon Philip Paty, and through this unique collaborative initiative, we have been able to identify novel radiosensitizers to take forward into phase 1 clinical trials with parallel co-clinical trials in patient-derived organoids. Further, we have improved our initial in vivo endoluminal rectal cancer model by translating it to the immunocompetent setting to better understand the biology contributing to chemoresistance and radioresistance in rectal cancer.
Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, Verheij FS, Omer DM, Lee M, Dunne RF, Marcet J, Cataldo P, Polite B, Herzig DO, Liska D, Oommen S, Friel CM, Ternent C, Coveler AL, Hunt S, Gregory A, Varma MG, Bello BL, Carmichael JC, Krauss J, Gleisner A, Paty PB, Weiser MR, Nash GM, Pappou E, Guillem JG, Temple L, Wei IH, Widmar M, Lin S, Segal NH, Cercek A, Yaeger R, Smith JJ, Goodman KA, Wu AJ, Saltz LB. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol. 2022 Apr 28:JCO2200032 [online ahead of print].
Choi SH, Kim JK, Chen CT, Wu C, Marco MR, Barriga FM, O’Rourke K, Pelossof R, Qu X, Chang Q, de Stanchina E, Shia J, Smith JJ, Sanchez-Vega F, Garcia-Aguilar J. Mol Cancer Res. 2022 Apr 8;molcanres.MCR-21-0994-A.2021 [online ahead of print].
Hsu KS, Adileh M, Martin ML, Makarov V, Chen J, Wu C, Bodo S, Klingler S, Sauvé CG, Szeglin BC, Smith JJ, Fuks Z, Riaz N, Chan TA, Nishimura M, Paty PB, Kolesnick R. Colorectal cancer develops inherent radiosensitivity that can be predicted using patient-derived organoids. Cancer Res. 2022 Apr 26:canres.4128.2021.
Ecker BL, Shin P, Saadat LV, Court CM, Balachandran VP, Chandwani R, Drebin JA, Jarnagin WR, Kingham TP, Soares KC, Vakiani E, Wei AC, Kemeny NE, Smith JJ, Gonen M, D’Angelica MI. Genomic stratification of resectable colorectal liver metastasis patients and implications for adjuvant therapy and survival. Ann Surg. 2022;275(2):371-381. PMCID: PMC8754193.
Kim JK, Wu C, Del Latto M. Gao Y, Choi S, Kierstead M, Sauve C, First C, Chaves Perez A, Sillanpaa J, Chen C, Lawrence K, Paty P, Barriga F, Shia J, Sawyers C, Lowe S, Garcia-Aguilar J, Romesser PB, * J. Joshua Smith.* A new immunocompetent rectal cancer model to study radiation therapy. bioRxiv 479335 [Preprint]. February 10, 2022. Available from: https://doi.org/10.1101/2022.02.07.479335
J. Joshua Smith, MD, PhD, FACS
- The Smith Lab studies rectal cancer, and we developed the first patient-derived rectal cancer organoids. These rectal cancer organoids recapitulate the clinical and molecular features of patients with rectal cancer and uniquely reflect the clinical responses to therapy of the patients from which they were derived.
- [email protected]
- Email Address
- R37 NCI MERIT Award for Early-Stage Investigators - National Cancer Institute (March 2020 to present))
- R37: Expansion of Tumoroid Models for Precise Treatment of Rectal Cancer Patient - National Cancer Institute (March 2020-present)
- Leveraging Radiation Induced Senescence (RIS) to Potentiate Anti-Tumor Immunity - Geoffrey Beene Cancer Center (2021-2022)
- Translational Platform for the Development, Characterization, and Clinical Assessment of Radiation Sensitizers in Rectal Cancer - Imaging and Radiation Sciences Program Seed Grant–MSK (2019-2021)
- 27th Franklin Martin, MD, FACS Faculty Research Fellowship - American College of Surgeons (2017-2019)
- ASCRS Career Development Award - American Society of Colon and Rectal Surgeons (2017-2019)
- 2016 Joel J. Roslyn Faculty Research Award - Association of Academic Surgery (February 2016)
- Michael E. Burt, MD, PhD, Award for Clinical Excellence - Memorial Sloan Kettering Cancer Center Department of Surgery (June 2015)
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J. Joshua Smith discloses the following relationships and financial interests:
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