RESEARCH OVERVIEW
Repetitive DNA sequences that comprise nearly half of the human genome are implicated in cancer development and as effectors of epigenetic therapies that augment cancer immunotherapy responses through ‘viral mimicry’ (Chen*, Ishak*, Cancer Discovery, 2021). However, the exact roles of repetitive elements as causative agents in cancer initiation or cancer immunotherapy response remain controversial and paradoxical (Ishak and De Carvalho, Annual Reviews in Cancer Biology, 2020). My research explores contributions of repetitive DNA elements in cancer initiation, progression, and therapeutic response to improve cancer immunotherapies and approaches for cancer interception and immunoprevention.
ISHAK LAB RESEARCH PROGRAM:
The overarching goal of the Ishak Lab is to uncover the roles of repetitive elements in cancer initiation, development, and therapeutic response to improve cancer immunotherapies and approaches for cancer interception and immunoprevention. Major research directions include the following:
1. Define roles of repetitive elements in cancer initiation and immune evasion
2. Define roles of repetitive elements in tumor suppression and cellular homeostasis
3. Leverage repeat RNA and proteins as targets for cancer interception and cancer immunotherapy
This research program will unite basic scientists, clinicians, and computational biologists who will characterize archived patient tissues and patient-derived primary cells to obtain direct insights into human disease. We will develop mouse models to uncover how repetitive elements promote cancer initiation, and test strategies to target repetitive elements as cancer immunotherapies and cancer-interception strategies. Our discoveries will be broadly applicable to the majority of cancers that express repetitive elements. This program will initially use ovarian high grade serous cancer (HGSC) as a model due to the nearly ubiquitous inactivation of TP53 as an initiating event, a tumor suppressor implicated in silencing repeats that is inactivated in nearly every human cancer.
The mission of the Ishak lab is to improve HGSC patient outcomes. Towards this mission, the lab will strive to translating our discoveries into clinical trials that explore augmentation of cancer immunotherapies or targeting retrotransposons as a cancer-interception strategy during premalignant windows of opportunity.
More importantly, the Ishak Lab will develop young scientists that will move on to flourishing careers that will benefit the scientific and medical communities. As a first-generation academic, I understand how access to opportunities can impact the trajectory of a student’s career. From this perspective, I will champion mentorship of all lab members, and offer sponsorship to trainees throughout the department.
ISHAK LAB RESEARCH PROGRAM:
The overarching goal of the Ishak Lab is to uncover the roles of repetitive elements in cancer initiation, development, and therapeutic response to improve cancer immunotherapies and approaches for cancer interception and immunoprevention. Major research directions include the following:
1. Define roles of repetitive elements in cancer initiation and immune evasion
2. Define roles of repetitive elements in tumor suppression and cellular homeostasis
3. Leverage repeat RNA and proteins as targets for cancer interception and cancer immunotherapy
This research program will unite basic scientists, clinicians, and computational biologists who will characterize archived patient tissues and patient-derived primary cells to obtain direct insights into human disease. We will develop mouse models to uncover how repetitive elements promote cancer initiation, and test strategies to target repetitive elements as cancer immunotherapies and cancer-interception strategies. Our discoveries will be broadly applicable to the majority of cancers that express repetitive elements. This program will initially use ovarian high grade serous cancer (HGSC) as a model due to the nearly ubiquitous inactivation of TP53 as an initiating event, a tumor suppressor implicated in silencing repeats that is inactivated in nearly every human cancer.
The mission of the Ishak lab is to improve HGSC patient outcomes. Towards this mission, the lab will strive to translating our discoveries into clinical trials that explore augmentation of cancer immunotherapies or targeting retrotransposons as a cancer-interception strategy during premalignant windows of opportunity.
More importantly, the Ishak Lab will develop young scientists that will move on to flourishing careers that will benefit the scientific and medical communities. As a first-generation academic, I understand how access to opportunities can impact the trajectory of a student’s career. From this perspective, I will champion mentorship of all lab members, and offer sponsorship to trainees throughout the department.
