Research in the Tong Lab
The Tong Lab is focused on studying the genetic progression of colorectal cancer, the 2nd leading cause of cancer-related deaths in the United States. The Tong Lab uses mouse and organoid models to study cancer progression both in vivo and in vitro. These systems provide powerful tools to uncover the molecular mechanisms of tumor initiation, invasion, and metastasis.
SMAD4/TGFβ in CRC
The SMAD4/TGFβ signaling pathway is mutated in over 60% of all cancers, and is associated with poor prognosis. In colorectal cancer, the loss of SMAD4 is a hallmark of late-stage cancers, and is correlated with metastatic disease. Our studies reveal that SMAD4 has a direct role in suppression tumor invasion and has a transcriptional role in regulating secretory and signaling pathways that impact extracellular space beyond the tumor. These findings indicate the role of SMAD4 in suppressing critical components of the tumor microenvironment which promote cancer progression. Uncovering these mechanisms will lead to potential new makers and targets for therapies.
Patient Derived Organoids for Translational Studies
In coordination with clinicians at Hackensack Meridian Health, the Tong Lab has established a workflow to derive colorectal cancer patient tumor organoids. With the capability to study individual patient cancers in an in vitro model system, we can assess drug response and determine what cell populations within specific tumors contribute to resistance and sensitivity. These studies will focus on generating a workflow to better understand and ultimately predict the optimal treatment regimens for individual patients.
Selected Publications
Kevin Tong, Oscar Pellón-Cárdenas, Veerin R. Sirihorachai, Bailey N. Warder, Om A. Kothari, Ansu O. Perekatt, Emily E. Fokas, Robert L. Fullem, Anbo Zhou, Joshua K. Thackray, Hiep Tran, Lanjing Zhang, Jinchuan Xing, Michael P. Verzi. Cell Rep. Degree of Tissue Differentiation Dictates Susceptibility to BRAF-driven Colorectal Cancer. 2017 Dec 26;21(13):3833-3845.
Kevin Tong, Om A. Kothari, Katherine S. Haro, Anshuman Panda, Manisha M. Bandari, Jillian N. Carrick, Joseph J. Hur, Lanjing Zhang, Chang S. Chan, Jinchuan Xing, Michael L. Gatza, Shridar Ganesan, Michael P. Verzi. Oncogene. SMAD4 is Critical in Suppression of BRAF-V600E Serrated Tumorigenesis. (2021).
Tong K, Bandari M, Carrick JN, Zenkevich A, Kothari OA, Shamshad E, Stefanik K, Haro KS, Perekatt AO, Verzi MP. In Vitro Organoid-Based Assays Reveal SMAD4 Tumor-Suppressive Mechanisms for Serrated Colorectal Cancer Invasion. Cancers (Basel). 2023 Dec 13;15(24):5820. doi: 10.3390/cancers15245820.
Simhadri S, Carrick JN, Murphy S, Kothari OA, Al-Hraishami H, Kulkarni A, Jalloul N, Stefanik K, Bandari M, Chettur K, Yao M, Ginjala V, Groisberg R, Hochster H, Mehnert J, Riedlinger G, Khiabanian H, Verzi MP, Tong K, Ganesan S. Evolution of Rapid Clonal Dynamics and Non-Cross-Resistance in Response to Alternating Targeted Therapy and Chemotherapy in BRAF-V600E-Mutant Colon Cancer. JCO Precis Oncol. 2024 Dec;8:e2300260. doi: 10.1200/PO.23.00260.