Aliyah Hirji
Pronouns: she/her
Research Mentor(s): Alnawaz Rehemtulla
Co-Presenter:
Research Mentor School/College/Department: Radiation Oncology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 1 – 10am – 10:50am
Room: League Ballroom
Authors: Aliyah Hirji, Dr. Alnawaz Rehemtulla
Presenter: 10
Abstract
Women with hormone receptor-positive, Her2-negative breast cancer (HR+/Her2-), are currently treated using CDK4/6 inhibitors in combination with endocrine therapy. However, all patients with metastatic breast cancer eventually progress and succumb to the disease due to the development of resistance. A poor understanding of the mechanisms that lead to the acquired resistance to CDK4/6 inhibitors has hampered the development of additional treatment strategies to extend the survival of this patient population. The kinase activity of CDK4/6 is a requisite for the entry of cells into the cell cycle and production of daughter cells. Inhibition of CDK4/6 therefore, results in arrest of cells in the G1-phase of the cell cycle. Resistance to CDK4/6 inhibition suggests that cancer cells utilize an alternative mechanism to enter the S-Phase of the cell cycle from the G1-Phase. Our laboratory has previously discovered that the FADD protein (Fas Associated Death Domain) overcomes CDK4/6 inhibition by forcing cells from G1 to S cell cycle phases. These experiments involve the use of genetically tagged cancer cells with engineered proteins that fluoresce green (in G1), red (in S) or yellow (in G2/M). Live videos of individual tagged cancer cells are acquired over three days and analyzed to determine the time it takes for cells to transition between each cell cycle phase (Green to Red to Yellow). I am using ImageJ and MATLAB to track individual cells in time-lapse films using artificial intelligence. The acquired data are used to create visual representations of cell cycle transition under different experimental conditions. To explore the effects of FADD on the cell cycle further, we are now analyzing data between the cell cycle phase transitions through MATLAB programming software. As we are just beginning to use MATLAB, we are still awaiting results, however, expect to see cells with higher levels of FADD to transition through the cell cycle more quickly than cells with lower levels of FADD. As we continue our research and discover more about the cell cycle in relation to cancer treatments, we hope to make a substantial discovery that can help patients in the clinic. If we find that FADD is the culprit behind resistance to CDK4/6 inhibitors, inhibition of FADD function could restore sensitivity to CDK4/6 inhibitors, thereby prolonging the survival time of cancer patients.
Biomedical Sciences, Interdisciplinary
