Programs
Departments & Divisions
Institutes and Centers
Professor
Department of Cell Systems and Anatomy
Greehey Children's Cancer Research Institute
Currently seeking M.S. & Ph.D. students.
The interest of our lab is to identify and understand mechanisms of damage survival and response. People who inherit a deficiency in damage response are predisposed to develop cancer, usually as children or young adolescents. Further, most cancer treatments are based on damaging cancer cells, so understanding why a chemotherapy works, and for which patients, should lead to more effective (targeted) and less toxic treatments that will increase the cure rate and improve quality of life for cancer survivors.
My research focus for the last 20 years has been on DNA repair and DNA damage response. For this my lab uses a variety of model systems, including in vivo mouse models and tissue culture systems. DNA damage response and repair is central to normal development and when aberrant, developmental defects, aging phenotypes and cancer ensue. Our work reflects these various aspects of DNA damage response and DNA repair biology, often taking what might be termed a systems biology approach. In general, we apply the knowledge we gain to understand how these processes relate to cancer development and treatment. For example, we recently elucidated that the chemosensitivity observed for Ewing sarcoma is due to protein interactions of the fusion oncogene EWS-FLI1 interfering with the normal biology of EWSR1, resulting in BRCA1 being trapped in a transcription complex and unavailable to promote DNA repair. These findings are a paradigm shift in our understanding of a disease that has largely been studied to understand how the EWS-FLI1 gene expression program drives the etiology of this cancer. This work was published in Nature. We have also published papers delineating how the NRF2 pathway responds to alkylation damage to protect against unfolded protein response, again building on our systems biology approaches. I have a particular interest in the ATM/p53/BRCA1 and NRF2 damage response pathways and how they relate to control of DNA replication, homologous recombination and cancers. Towards this end, we have a tremendous set of resources to evaluate DNA repair and damage response and expertise in RNAi, CRISPR, gene expression, ChIP, protein interactions, bioinformatics, DNA combing, transcription stress and metabolomics available.
Related diseases: Cancer, Ewing sarcoma, breast cancer, Ataxia telangiectasia, Bloom syndrome, Li-Fraumeni
Techniques: Cell biology, molecular genetics, RNAi, CRISPR, gene expression, ChIP, protein interactions, mouse genetics, cancer xenografts, bioinformatics, DNA combing, transcription assays as well as metabolic flux, oxygen flux assays and metabolomics
2020 Became a full member of the NIH MCT1 study section.
2018 Mays Cancer Center 2018 Discovery of the Year
2017 Member of the UT Shine Academy
2015 Member UT Health Science Center of San Antonio’s Academy of Master Teachers
2015 UT Health Science Center of San Antonio 2015 Presidential Teaching Excellence Award
2010 Cellular and Structural Biology Award for Excellence in Graduate Student Education
DNA repair, damage response, Breast Cancer, Pediatric Cancer (Ewing sarcoma), Genetic syndromes, System biology and Metabolism
The interest of our lab is to identify and understand mechanisms of damage survival. People who inherit a deficiency in damage response are predisposed to develop cancer, usually as children or young adolescents. Further, most cancer treatments are based on damaging cancer cells, so understanding why a chemotherapy works, and for which patients, should lead to more effective and less toxic treatments that will increase the cure rate and improve quality of life for cancer survivors.
STATE:
Funding Agency: CPRIT RTA RP170345 (PI: Oyajobi, Role: CoI) 12/01/16 - 11/20/21
Title: UTHSCSA Cancer Research Training Program
Role: CoI % Effort: 5
Total Costs: $3,996,895
Research Training Award supports for pre-doctoral, post-doctoral trainees, and summer (undergraduate) students, as part of a comprehensive training program covering all aspects cancer research.
FEDERAL:
Funding Agency: NIH NCI 1R01CA241554 Period: 5/2020 - 4/2025
Title: Dysregulated transcription processes in Ewing sarcoma
Role: PI % Effort: 20
Total Costs: $1,634,541
To determine the consequences of dysregulated transcription regulation in Ewing’s sarcoma.
PRIVATE:
Project #: Collaborative Research Grant (PI: Bishop) 11/2019 - 10/2021
MERCK EMD Serano $538,000
Title: Assessing the pathological accumulation of R-loops in cancer as an indication of sensitivity to RNA splicing inhibition
To identify whether R-loops levels can be used to indicate a defect in splicing in different types of cancer and sensitivity to spliceosome inhibitors.
Project #: 614252: Childhood Cancer Research Grant (PI: Bishop) 01/2019 - 12/2020
The Andrew McDonough B+ Foundation $150,000
Targeting RNA processing defects of Ewing sarcoma
Role: PI % Effort: 15
To follow up on initial validations of a previously conducted RNAi screen that identified splicing components as synthetic lethal target in Ewing sarcoma. The aim is to then evaluate splicing inhibitors that have the same effect as RNAi depletion of splicing genes and if a therapeutic window exists that can that suggests these inhibitors can be used in the treatment of Ewing sarcoma.
Project #: GCCRI Exploratory experimental fund (PI: Bishop) Period: 9/2019 - 8/2020
Funding Agency: GCCRI funds Total $10,000
Title: Metabolomics in ATM inhibited cells
Role: PI % Effort: N/A
To perform an isotope tracing metabolomics experiment in cells +/- ATM inhibitor to follow glucose and glutamine utilization.
Project #: GCCRI (PI: Bishop) (NCE to 2/2020) Period: 5/2017 - 4/2019
Funding Agency: GCCRI funds Total $100,000
Title: Targeting the transcription dysregulation of Ewing sarcoma
Role: PI % Effort: N/A
Total Direct Costs: $100,000
To validate a previously conducted RNAi screen for synthetic lethal viability in Ewing sarcoma with a focus on determinants of transcription regulation. The goal is to identify therapeutic targets that can be used in the treatment of Ewing sarcoma.
Funding Agency: IIMS (PI:Bishop) (NCE to 09/2018) Period: 10/2014 - 09/2015
Title: Bloom syndrome, chronic stress and cancer
Role: PI % Effort: N/A
Total Costs: $50,000
To determine the metabolic alterations associated with BLM deficiency and whether altering these changes with appropriate interventions can reduce some of the associated cellular and organismal phenotypes with BLM deficiency.
Project #: Ambassador’s Circle Research Award (NCE to 01/2021) Period: 02/2012 - 01/2013
Funding Agency: GCCRI Ambassador’s Circle
Title: Targeting nucleotide pools in Bloom’s cells
Role: Principal Investigator % Effort: N/A
PGID: 152219
Total Direct Costs: $25,000
We propose to examine the nucleotide pool changes associated with Bloom syndrome cells.
FELLOWSHIPS TO STUDENTS AND POSTDOCTORAL FELLOWS:
Project #: 2020 Greehey Graduate Fellowship Award Period: 09/2020 - 08/2021
Funding Agency: Graduate Dean’s Office (Predoctoral Traineeship Award to Henry Miller)
Title: Systems analysis to identify novel vulnerabilities in Ewing sarcoma
Role: Mentor % Effort: N/A
Total Costs: $33,600
To identify novel targets to therapeutically treat Ewing sarcoma.
Project #: 2020 MCC Graduate Fellowship Award Period: 09/2020 - 08/2021
Funding Agency: Mays Cancer Center (Predoctoral Traineeship Award to Kevin Kanda)
Title: Ewing Sarcoma relies on Endogenous Cysteine and Glutamine for Antioxidant Response
Role: Mentor % Effort: N/A
Total Costs: $33,600
To elucidate the basis and potential therapeutic value of the metabolic dysregulation of amino acids in Ewing sarcoma.
Project #: 2020 CPRIT Training Grant Fellowship Award Period: 10/2020 - 09/2021
Funding Agency: CPRIT Training Grant (Fellowship Award to Pramiti Mukhopadhyay)
Title: Dedifferentiation in Ewing sarcoma mediated by R-loops preserves genomic integrity
Role: Mentor % Effort: N/A
Total Costs: $30,600
To evaluate replication stress during the dedifferentiation process of Ewing sarcoma.
Project #: CDMRP PRCRP Horizon Award Period: 07/2019 - 06/2021
Funding Agency: DoD (Predoctoral Traineeship Award to Liesl Lawrence)
Title: Transcription, R-loops and RNA Splicing in Ewing Sarcoma
Role: Mentor % Effort: N/A
Total Costs: $150,000
Understanding and targeting altered regulation of transcription and splicing in Ewing sarcoma.
Project #: 2018 AACR-AstraZeneca START Period: 09/2018 - 08/2021
Funding Agency: AACR-AstraZeneca (Postdoctoral Traineeship Award to Aparna Gorthi)
Title: Identifying modifiers of PARP1 inhibitor sensitivity in BRCA-like tumors
Role: Mentor % Effort: N/A
PGID: 429203
Total Costs: $225,000
To identify targets that will improve the efficacy of PARP1 inhibition in tumors that have BRCA1 like phenotypes (eg. Ewing sarcoma).
2017 – present CSA Faculty Forward Committee Chair
2014 - present CSB Teaching Currency Committee Member
2013 - present CSB Teaching Award Committee Member
2014 - present CSB Postdoc Award Committee Member
2020 - present IBMS Program Director Search Committee Member
2020 - present GCCRI Director Search Committee Member
2020 – present IMBS Curriculum Committee Chair
2014 – present Cancer Biol Discipline Committee of Graduate Studies Member
2020 - present Sarcoma Working Group Organizer
2020 - present Subcommittee to organize GCCRI Symposium 2021 Member
2019 - present GCCRI Seminar Series Committee Member
2017 – present UT Shine Awards Committee Member
2015 - present CTRC CPRIT Review Committee Member
2012 – Present GCCRI Operations Committee Member
2005 – Present GCCRI Radiation Use and Safety Coordinator
2011 – present Ewing’s Sarcoma Biology Committee Member in Children's Oncology Group