Mercurio Lab News
Ayush Kumar has successfully defended his PhD thesis on Uncovering the Mechanisms that Drive Resistance to Radiation Therapy in Triple-Negative Breast Cancer. Ayush will be returning to his 3rd year of medical school to complete his clinical rotations. We are all so proud of everything you have accomplished thus far and are so happy to have been a part of your MD/PhD journey! Congratulations Ayush!
Photos of our celebration can be found on the Mercurio Lab Events page!
Third-year M.D./Ph.D. student Boris Dimitrov is officially a Ph.D candidate at UMass Chan Medical School. His current research is focused on how ferroptosis resistance is used by cancer cells during metastasis initiation. Congrats Boris!
Prajakta Ambegaokar has joined the lab!
Prajakta is a third year graduate student at UMass Chan Mecical School.
We are excited to have you on the team! Welcome!
Out of 1,330 entrants, Ayush Kumar has been selected as the winner of the 2024 AMA Research Challenge for his work on Enhancing the radiosensitivity of triple-negative breast cancer by targeting VEGF/Neuropilin-2.
You can read more about Ayush’s journey to winning the contest, as well as watch the video of the impressive work presented by all 5 finalists in the competition!
ABSTRACT
Although programmed cell death ligand 1 (PD-L1) is best known for its role in immune suppression, tumor-intrinsic functions are emerging. Here, we report that tumor cells that express PD-L1 are sensitive to ferroptosis inducers such as imidazole ketone erastin (IKE). PD-L1 promotes ferroptosis sensitivity because it suppresses SLC7A11 expression and diminishes glutathione levels. Although the use of anti-PD-L1 antibody drug conjugates (ADCs) could be effective for the delivery of ferroptosis inducers to specific tumor populations, the chemistry of most ferroptosis inducers precludes their incorporation in ADCs. To overcome this challenge, we synthesized an antibody nanogel conjugate (ANC) comprised of an anti-PD-L1 antibody conjugated to a nanogel encapsulated with IKE. This ANC targets PD-L1-expressing cells in vitro and in vivo and induces ferroptosis, resulting in tumor suppression. Importantly, this approach is superior to systemic administration of IKE because it enables enhanced delivery of IKE specifically to tumor cells and it requires lower drug doses for efficacy.
Wang M, Prachyathipsakul T, Wisniewski CA, Xiong C, Goel S, Goel HL, Karner ER, Mukhopadhyay D, Gupta P, Majee A, Thayumanavan S, Mercurio AM. Therapeutic induction of ferroptosis in tumors using PD-L1 targeting antibody nanogel conjugates. Cell Chem Biol. 2024 Nov 26.
