Current advisor: Joshua B. Rubin, MD, PhD
Undergraduate university: University of California – Berkeley
Nearly all complex human diseases exhibit some degree of sex difference in incidence, age of onset, disease severity, and/or response to treatment, and this includes brain tumors. Males have increased incidence and decreased survival for the majority of brain tumor types, a finding that spans cultures, ages, and even species. My research includes three main projects, which together explore how male and female differences across different biological scales contribute to sex differences in brain tumor risks and outcomes. The first project focuses on the genetic/epigenetic scale; we found that male and female glioblastoma cells differ in the distribution of Brd4-bound active enhancers, which results in different transcriptional states and opposing effects of epigenetic drugs targeting Brd4. The second project focuses on the cellular scale; we found that female glioblastoma cells are more sensitive to p21-induced cellular senescence following irradiation, and that sex differences in p21 sensitivity are patterned by exposure to gonadal hormones in utero. The third project focuses on the tissue scale; we found that brain tumors from women with previous pregnancies contain fetal microchimeric cells within the tumor microenvironment, a phenomenon unique to women, with potential implications for immune regulation and immunotherapy. As a whole, this body of work demonstrates how sex differences in brain tumor biology are encoded at every level, from the genetic scale to the systemic scale. As we move towards more personalized medicine approaches to treatment, it will be critical to incorporate sex in the design of clinical trials and in the implementation of therapies in clinical practice if we are to maximize treatment success for all patients, male and female.
Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma.
Broestl L, Warrington NM, Grandison L, Abou-Antoun T, Tung O, Shenoy S, Tallman MM, Rhee G, Yang W, Sponagel J, Yang L, Kfoury-Beaumont N, Hill CM, Qanni SA, Mao DD, Kim AH, Stewart SA, Venere M, Luo J, Rubin JB. 2022 Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma. Commun Biol, 5(1):781.
Kfoury N, Qi Z, Prager BC, Wilkinson MN, Broestl L, Berrett KC, Moudgil A, Sankararaman S, Chen X, Gertz J, Rich JN, Mitra RD, Rubin JB. 2021 Brd4-bound enhancers drive cell-intrinsic sex differences in glioblastoma. Proc Natl Acad Sci USA, 118(16):e2017148118.
Broestl L, Rubin JB. 2021 Sexual differentiation specifies cellular responses to DNA damage. Endocrinology, ():epub ahead of print.
Rubin JB, Lagas JS, Broestl L, Sponagel J, Rockwell N, Rhee G, Rosen SF, Chen S, Klein RS, Imoukhuede P, Luo J. 2020 Sex differences in cancer mechanisms. Biol Sex Differ, 11(1):17.
Broestl L, Rubin JB, Dahiya S. 2018 Fetal microchimerism in human brain tumors. Brain Pathol, 28(4):484-494.
Broestl L, Rubin J, Dahiya S. (2016) Fetal Microchimerism in Human Brain Tumors. Society for Neuro-Oncology Annual Meeting, Scottsdale, AZ, Abstract.