Francisco J. Sánchez-Rivera, PhD

Francisco Sanchez-Rivera

Credit: Adam Lerner

Assistant Professor of Biology

Pilot Member, Ludwig Center at MIT

Howard Hughes Medical Institute Hanna H. Gray Fellow 

Contact Information

Francisco J. Sánchez-Rivera

76-361A

(617) 715-3389

Administrative Support

Julia Liberman

(617) 253-6425

Research Areas

Metastasis, Precision medicine

While cancers are often associated with specific mutations, some alterations cause disease only in a subset of individuals. I want to learn why this is and how it is determined.

Research Summary

The long-term goal of the Sánchez-Rivera laboratory is to elucidate the cellular and molecular mechanisms by which genes and disease-predisposing mutations interact with and within an individual’s genome to influence the development of diseases like cancer. To do so, we employ increasingly sophisticated genome editing technologies to engineer and manipulate the DNA of cells and organisms with single nucleotide precision.

Focusing on cancer as a model genetic disease, and genes that exhibit functional and mutational variation as prototypes, we are pursuing three overarching goals. First, we are investigating how genes and mutations interact at the cellular and molecular levels depending on context (e.g. tissue type). These studies will provide insights into why certain genetic lesions drive disease in some settings, but not others, and test the hypothesis that specificity arises from cellular and molecular programs that are differentially engaged in a context-specific manner. Second, we are probing how genetic background influences disease initiation and progression. Here, we test the hypothesis that germline variation in coding and non-coding regions functionally shapes the disease-causing potential of common genetic lesions. Lastly, we are investigating the molecular mechanisms by which genes and other DNA sequences functionally interact to influence these phenotypes. These studies will address why some genes and non-coding regions are overwhelmingly associated with disease, and investigate whether common disease-associated mutations are strongly selected due to functional specialization or stochastic mutagenic processes. The questions addressed by these three research directions will define mechanisms with fundamental and clinical importance that could be leveraged to design more precise genome-informed cancer therapies. More broadly, we expect that our framework will produce generalizable concepts and approaches that could shed light on the development and treatment of genetic diseases beyond cancer and bridge the gap between correlation and causality.

Biography

Francisco J. Sánchez-Rivera was born and raised in Mayagüez, Puerto Rico. He obtained his bachelor’s degree in Microbiology from the University of Puerto Rico at Mayagüez and his PhD in Biology from MIT. As a PhD student with Tyler Jacks, he was among the first to use CRISPR to rapidly and systematically interrogate cancer drivers in vivo and to identify genotype-specific dependencies in lung adenocarcinoma. As a HHMI Hanna H. Gray Fellow with Scott W. Lowe at MSKCC, he developed and applied CRISPR base editing methods to engineer mutations with high efficiency and precision in cells and tissues of living animals to quantitatively interrogate cancer variants at scale, as well as approaches to chart tumor evolution using CRISPR and single cell RNA sequencing. Sánchez-Rivera joined the MIT faculty in 2022 as an assistant professor in the Department of Biology and a member of the Koch Institute. He is a recipient of a V Scholar Grant from the V Foundation.

See list of publications

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