Professor of Microbiology and Immunology in Obstetrics and Gynecology
Our research seeks to understand the molecular and metabolic programs that dictate immune cell function in health and disease. We are interested in defining how molecular pathways that sense organelle stress direct the immune system in cancer, inflammation, autoimmunity, and infectious diseases.
Mounting optimal immune responses against malignant cells and pathogens requires high levels of protein synthesis, folding, modification, and trafficking in leukocytes, which are processes coordinated by the endoplasmic reticulum (ER). However, diverse extracellular and intracellular conditions can affect the protein-handling capacity of this organelle, inducing a state of ‘ER stress’ that activates the unfolded protein response (UPR). Our research has provided key insights into the role of ER stress response pathways in immunity, revealing its context-dependent impact on immune cell metabolism, function, and fate. We uncovered that activation of ER stress sensors can stimulate lipogenesis and prostaglandin biosynthesis in myeloid cells. Further, we established that in T cells experiencing nutrient restriction, the activation of ER stress sensors can regulate mitochondrial function and bioenergetics. Dysregulation of the UPR in immune cells can therefore contribute to various pathologies such as cancer, chronic pain, autoimmunity, inflammation, and metabolic disorders. Targeting abnormal ER stress responses has emerged as a promising approach to control or restore immune cell function in diverse pathological conditions. Our laboratory is interested in answering multiple questions relevant to the role of ER stress in immunity, with an emphasis on defining how the tumor microenvironment causes ER stress in multiple cell populations to evade immune control.
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Biography
Dr. Juan R. Cubillos-Ruiz is a tenured Professor of Microbiology and Immunology whose research is defining how organelle stress responses regulate immune cell function in health and disease. Trained in microbiology and immunology, he pioneered approaches to decipher the role of endoplasmic reticulum and mitochondrial stress responses in cancer, inflammation, infectious diseases, and pain. Since joining the faculty in 2015, his work has received major honors and sustained support from federal agencies and philanthropic foundations. Dr. Cubillos-Ruiz holds The Bruce Laine Ballard MD Award for Excellence in Mentorship and has been recognized as a Diversity Pioneer by Weill Cornell Medicine.
Distinctions:
LOTUS Ovarian Cancer Challenge Award, Pershing Square Foundation.
The Bruce Laine Ballard, MD Award for Excellence in Mentorship. Weill Cornell Medicine.
Irma Hirschl Career Scientist Award - The Irma T. Hirschl/Monique Weill-Caulier Charitable Trust.
The William J. Ledger, M.D., Endowed Professorship for Infection and Immunology in Obstetrics and Gynecology. Weill Cornell Medicine – Cornell University.
Pershing Square Sohn Prize for Young Investigators in Cancer Research.
Schreiber Prize for Outstanding Mentored Investigators, Ovarian Cancer Research Alliance.
Ovarian Cancer Academy–Early-Career Investigator Award, Department of Defense.
Wade F.B. Thompson CLIP Investigator, Cancer Research Institute.
Cancer Research Institute – Irvington Institute, Postdoctoral Fellowship.
John H. Copenhaver, Jr. and William H. Thomas, MD 1952 Predoctoral Fellowship, Dartmouth Medical School.
Sandoval, T.A., Salvagno, C., Chae, C., Awasthi, D., Giovanelli, P., Marin Falco, M., Hwang, S., Teran-Cabanillas, E., Suominen, L., Yamazaki, T., Kuo, H., Moyer, J.E., Martin, M.L., Manohar, J., Kim, K., Sierra, M.A., Ramos, Y., Tan, C., Emmanuelli, A., Song, M., Morales, D.K., Zamarin, D., Frey, M.K., Cantillo, E., Chapman-Davis, E., Holcomb, K., Mason, C.E., Galluzzi, L., Ni Zhou, Z., Vähärautio, A., Cloonan, S.M., Cubillos-Ruiz, J.R., ; Iron Chelation Therapy Elicits Innate Immune Control of Metastatic Ovarian Cancer.Cancer Discov 1 October 2024; 14 (10): 1901–1921.
Awasthi, D., Chopra, S., Cho, B. A., Emmanuelli, A., Sandoval, T. A., Hwang, S. M., Chae, C. S., Salvagno, C., Tan, C., Vasquez-Urbina, L., Fernandez Rodriguez, J. J., Santagostino, S. F., Iwawaki, T., Romero-Sandoval, E. A., Crespo, M. S., Morales, D. K., Iliev, I. D., Hohl, T. M., & Cubillos-Ruiz, J. R. (2023). Inflammatory ER stress responses dictate the immunopathogenic progression of systemic candidiasis.The Journal of clinical investigation, 133(17), e167359.
