Co-director, Experimental Therapeutics Program, UMGCCC
Education and Training
- 1979 - A Levels, Camden School for Girls, London, UK
- 1983 - B.Sc., University College London, London, UK, Honors in Human Genetics
- 1990 - Ph.D., Royal Post-Graduate Medical School, University of London, London, UK, Biological Sciences
Post-Graduate Education and Training
- 1990-1994 - Post-Doctoral Fellowship, Section of Hematology/Oncology, University of Chicago
- 1994-1996 - Research Associate, Section of Hematology/Oncology, University of Chicago
- 1996-1998 - Research Associate - Assistant Professor, Section of Hematology/Oncology, University of Chicago
- 1998-2005 - Lecturer, King’s College School of Medicine, Guy’s Campus, London, UK
- 1998-2005 - Head, Genomic Instability Laboratory, King’s College School of Medicine, Guy’s Campus, London, UK
- 2005-present - Associate Professor, University of Maryland School of Medicine, Baltimore
- 2015-present - Adjunct Associate Professor, VARI’s Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan
- 2016 - Awarded Tenure, Department of Radiation Oncology, UMSOM
- 2019 - Full Professor
Feyruz V. Rassool, PhD, received her doctorate at the Royal Postgraduate Medical School, University of London, UK. She did her postdoctoral training at the University of Chicago and assumed her first independent faculty position studying DNA damage and repair in myeloid malignancies at King’s College London. She has been at the University of Maryland for the last 12 years.
She is an expert in repair of potentially lethal forms of DNA damage, DNA double-strand breaks (DSBs), that play a critical role in generating genomic instability in cancer. Her work has specifically focused on the aberrant expression and activity of these repair pathways in cancer and leukemia cells that not only play a role in genomic instability, but also appear critical for cancer cell survival. These DNA repair components are attractive therapeutic targets. Thus, Dr. Rassool’s work provides a framework for the development and translation of novel therapeutic strategies for patients with leukemia’s and other cancers. Her recent work is focused on targeting DNA repair abnormalities in Cancer and leukemia.
Dr Rassool recently received the Ziskin Award to study the intersection between DNA damage and repair and epigenetic pathways in cancer and she is part of the SU2C stand-up to cancer Epigenetics Dream Team.
Studies to target acute myeloid malignancies and triple negative breast cancers with a combination of DNA repair and epigenetic inhibitors was recently published in Cancer Cell (2016). These studies are the basis for a clinical trial in AML led by Dr Maria Baer, Director of hematologic malignancies at UMGCCC.
DNA damage and repair, genomic instability, targeting DNA repair abnormalities
Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R, Pappou E, Harris J, Yen RW, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow CA. Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells. Cancer Cell 2012:21(3):430-46. doi: 10.1016/j.ccr. 2011.12.029. PMID: 22439938.
Tobin LA, Robert C, Rapoport AP, Gojo I, Baer MR, Tomkinson AE, Rassool FV. Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias (link). Oncogene 2013:32(14):1784-93. doi: 10.1038/onc.2012.203. PMID: 22641215.
Muvarak N, Kelley S, Robert C, Baer MR, Perrotti D, Gambacorti-Passarini C, Civin C, Scheibner K, Rassool FV. Role of C-MYC in DSB repair in tyrosine kinase activated leukemias. Mol Cancer Res. 2015 Apr;13(4):699-712. doi: 10.1158/1541-7786.MCR-14-0422. Epub 2015 Mar 31. PMID:25828893.
Muvarak N, Chowdhury K, Xia L, Robert C, YongE, Cai Y, Bellani M, Zou Y, Singh ZN, DuongVH, Rutherford T, Nagaria P, Bentzen SM, Seidman MM, Baer MR, Lapidus RG, BaylinSB, Rassool FV. Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA Demethylating Agents – A Potential Therapy for Cancer, Cancer Cell. 2016 Oct 10;30(4):637-650. doi: 10.1016/j.ccell.2016.09.002.PMID: 27728808.
Limin Xia, Wenjie Huang, Marina Bellani, Michael M. Seidman, Kaichun Wu, Daiming Fan, Yongzhan Nie, Yi Cai, Yang W. Zhang, Li-Rong Yu, Huili Li, Cynthia A. Zahnow,Wenbing Xie, Ray-Whay Chiu Yen, Feyruz V. Rassool*, Stephen B. Baylin*. CHD4 Acts As An Oncogene With A Driver Role For Initiating And Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes. CANCER-CELL-D-16-00726, accepted for publication.
* denotes co-senior author status.
Rassool FV, Gaymes TJ, Omidvar N, Brady N, Beurlet S, Pla M, Reboul M, Lea N, Chomienne C, Thomas NS, Mufti GJ, Padua RA. Reactive oxygen species, DNA damage, and error-prone repair: a model for genomic instability with progression in myeloid leukemia? Ca Res 2007:67(18):8762-71. PMID: 17875717.
Sallmyr A, Tomkinson AE, Rassool FV. Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks. Blood 2008:112(4):1413-23. doi: 10.1182/blood-2007-07-104257. PMID: 18524993.
Fan J, Li L, Small D, Rassool F. Cells expressing FLT3/ITD mutations exhibit elevated repair errors generated through alternative NHEJ pathways: implications for genomic instability and therapy. Blood 2010:116(24):5298-305. doi: 10.1182/blood-2010-03-272591. PMID: 20807885.
Li L, Zhang L, Fan J, Greenberg K, Desiderio S, Rassool FV*, Small D*. Defective non-homolo-gous end-joining blocks B-cell development in FLT3/ITD mice. Blood 2011:117(11):3131-9. doi:10.1182/blood-2010-05-286070. PMID: 21228325.
Tobin LA, Robert C, Nagaria P, Chumsri S, Twaddell W, Ioffe OB, Greco GE, Brodie AH, Tomkinson AE, Rassool FV. Targeting abnormal DNA repair in therapy-resistant breast cancers (link) Mol Cancer Res 2012:10(1):96-107. doi: 10.1158/1541-7786.MCR-11-0255. PMID: 22112941.
Dr Rassool’s work focuses on repair of potentially lethal forms of DNA damage, DNA double strand breaks (DSBs). She reported that an abnormal and highly error-prone version of DSB repair in cancer cells plays a critical role in generating genomic instability. In addition, this abnormal repair pathway appears critical for the survival of leukemia cells but not normal cells, and thus may be an attractive therapeutic target. Importantly, Dr Rassool’s work provides a framework for the development of novel therapeutic strategies in leukemias and other cancers in which abnormal DSB repair is observed.
Both in collaboration and independently, Dr Rassool has extended her work to the development of therapeutic strategies in leukemias and breast cancers that are resistant to standard therapies. One important collaborator in her efforts to target abnormal repair in therapy resistant breast cancer, is the world famous breast cancer researcher at the University of Maryland, Dr Angela Brodie. In their recently published manuscript in Molecular Cancer Research, they demonstrated that hormone therapy-resistant breast cancer cells exhibit significantly increased abnormal repair involving DNA ligase IIIa and poly ADP ribose polymerase (PARP-1), and that these cells are highly sensitive to a combination of PARP and DNA ligase III inhibitors. These results suggest that abnormal DSB repair may serve as biomarkers to identify tumors that are candidates for this therapeutic approach. Importantly, this recently published study was selected to be featured in the "MOLECULAR CANCER RESEARCH Highlights”.
Her work has also involved mechanisms by which embryonic stem cells (ESCs) maintain genomic integrity in response to environmental stress, compared with differentiated cells. Her lab has recently reported that human embryonic stem cells (hESCs) employ at least two strategies to maintain genomic integrity: First, they maintain enhanced levels of DSB repair transcripts and proteins and have high repair efficacy, as evidenced by established NHEJ assays. Second, they are highly sensitive to DNA damage, as evidenced by a high level of apoptosis upon irradiation. Importantly, adult somatic cells, “reprogrammed” to “dedifferentiate” into induced Pluripotent Stem Cells (iPSCs), mimic hESCs in their repair protein expression and repair efficacy, indicating that their DDR pathways are reprogrammed to resemble those of hESCs. In contrast, the differentiated parental cells from which iPSCs are derived have decreased expression of DSB repair components and demonstrate low repair activity and efficacy. Importantly, we have demonstrated that the DNA damage response is an important biomarker for successful reprograming of adult cells into pluripotent stem cells (IPSCs). This work is vital to the future use of IPSCs in regenerative medicine and has resulted in a published manuscript and RO1-equivalent funding from the Maryland Stem Cell Fund.
Most recently, and inspired by the Laura Zisken award in 2012, Dr Rassool has shown that DNA repair and epigenetic pathways interact and that a combination of DNA methyltransferase inhibitors and PARP inhibiotrs work synergistically to trap more PARP, leading to dramatic anti-tumor effects in AML and breast cancers with intact BRCA genes. This work was recently published in Cancer Cell (2016) and has led to a clinical trial in AML funded by the SU2C.
Dr Rassool received the Ziskin Award in 2012 to study the intersection between DNA damage and repair and epigenetic pathways in cancer and she is part of the SU2C stand-up to cancer Epigenetics Dream Team.
07/01/14 - 06/30/18
(Co-Inv., 5%; PI - M. Baer)
“Inhibition of Pim Kinases in Acute Myeloid Leukemia”
VA Merit Review Award
Role: To investigate role of Pim kinase inhibitors in DNA repair in leukemia.
10/01/14 - 09/30/17
(Co-Inv., 10%; PI - S. Baylin (JHU)
“Bringing Epigenetic Therapy to the Management of Ovarian and Other Cancers”
Adelson Foundation (Pilot)
Role: To investigate the role of PARP inhibitors and epigenetic drugs in ovarian cancer.
11/01/14 - 10/30/17
(Co-Inv., 10%); PI - S. Baylin (JHU)
“Clinical Trials for the Combined Use of DNA Demethylating Agents and PARP Inhibitors in Acute Myelogenous Leukemia”
Van Andel-SU2C, Inc.
Role: To investigate the role of PARP inhibitors and epigenetic drugs in ovarian cancer.
07/01/15 - 02/28/17
“Mechanisms for sensitivity to PARP inhibitors in cancer involving ALT NHEJ”
NIH - R21 5R21CA186974-02
10/1/15 - 9/30/18
“DNA Demethylating Agent and PARP Inhibitor Therapy Targeting Aberrant DNA Repair in Acute Myeloid Leukemia (AML)”
Leukemia & Lymphoma Society
11/1/16 - 10/30/17
(Co-Inv., 10%; PI Baer)
“A Phase I/II Multicenter Study Combining Guadecitabine, a DNA Methyltransferase Inhibitor, with Atezolizumab, an Immune Checkpoint Inhibitor, in Patients with Intermediate or High-risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia.”
Van Andel-SU2C, Inc.
Role: Provide correlative studies for clinical trial.
07/01/17 - 6/30/19
“Mechanisms for sensitivity to HDAC inhibitors involving PARP trapping in leukemias”
NIH - R21
New Treatment Combination Could Work Against Broader Array of Cancer Cells, Study Finds
Date: October 11, 2019
Author: Deborah Kotz
University of Maryland School of Medicine Researchers Find Two Drugs Work Together to Disrupt Cancer Cells’ Ability to Survive
In continuing efforts to find novel ways to kill cancer cells, researchers at the University of Maryland School of Medicine (UMSOM) have identified a new pathway that leads to the destruction of cancer cells. The new finding, published this week in the journal PNAS, could pave the way for the broader use of a class of anticancer drugs already on the market. These drugs, known as PARP inhibitors, are currently approved by the FDA to treat only a limited group of breast and ovarian cancers associated with BRCA gene mutations.
In a proof of concept study, the researchers demonstrated that combining a PARP inhibitor with a DNA methyltransferase (DNMT) inhibitor delivered a one-two punch to non-small cell lung cancer tumors, which are normally not associated with mutations in BRCA genes. The research, conducted in mouse models and cell lines, outlines the mechanistic action of the combination. The DNMT inhibitor triggers an effect that mimics a BRCA mutation in the cancer cell so the cell responds to the lethal effects of the PARP inhibitor, which prevents repair of damage to a tumor cell’s DNA, triggering cell death...
New Drug Combination Targets Aggressive Blood Cancer
Date: March 7, 2017
Source: Van Andel Research Institute
Published by: ScienceDaily
A pair of drugs that may be a one-two punch needed to help combat acute myeloid leukemia (AML), an aggressive blood cancer that kills nearly three-fourths of patients within five years of diagnosis, is the focus of a new multi-center clinical trial that will enroll patients at three sites across the U.S.
The trial pairs an investigational PARP inhibitor, talazoparib, with the DNA methyltransferase (DNMT) inhibitor decitabine, which is already approved for the treatment of myelodysplastic syndrome (MDS), a disease that often precedes AML. Preclinical studies show that combining the drugs may maximize their ability to kill cancer cells.
“Long-term survival with AML is quite poor and, unfortunately, our arsenal for treating it has remained largely unchanged for decades,” said Feyruz Rassool, Ph.D., an associate professor of radiation oncology at the University of Maryland School of Medicine, a researcher at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, and a member of the Van Andel Research Institute–Stand Up To Cancer (VARI–SU2C) Epigenetics Dream Team. “Combination therapies, such as talazoparib and decitabine together, allow us to attack cancer from multiple angles at the most basic level for a greater potential effect.”
Institutional Service – University of Maryland School of Medicine
- 2006-2011: Reviewer, American Cancer Society (ACS) Institutional Review Grant (IRG), Pilot Project Grants at the University of Maryland Greenebaum Cancer Center (served 1x annually)
- 2007-present: Member, Cancer Biology Curriculum Committee
- 2008-2013: Organizer, Free Radical Interest Group (FRIG) monthly seminars (year round)
- 2009-present: Member, Graduate Program in Life Science (GPLS) Curriculum Committee
- 2009-present: Member, Master’s Curriculum Committee
- 2009-2011: Member, School of Medicine Council
- 2011-2012: Interim Director, Radiobiology Department
- 2011-present: Member, T32 Cancer Biology Steering Committee
- 2012-present: Member, Master’s Program in Translational Research, Core Course
- 2013-present: Member, Translation Laboratory Sciences Advisory Committee
- 2013-present: Reviewer, T32 Grants (1x annually)
- 2013: Reviewer, Seed Grant Program UMB and UMCP (served 1x)
- 2014: Reviewer, Dean’s Challenge Grant (served 1x)
- 2015: Reviewer, Graduate Application for Graduate Program in Toxicology (serve 1x)
- 2015: Reviewer, Graduate Application for Graduate Program in Biochemistry (serve 1x)
- 2015-present: Member, Funding Submission Peer Review Committee, Radiation Oncology
- 2005: Moderator, Chromosomes and Cancer: From Translocations to Targeted Therapies, University of Chicago (served 1x)
- 2006: Chair Person, Baltimore Area Repair Symposium (BARS) – raised $15,000 (served 1x)
- 2008: Moderator, Myelodysplastic Syndromes: Pre-clinical and Translational Science, Baltimore Area Repair Symposium (BARS) (served 1x)
- 2008: Chair, DNA Damage and Repair Session, American Society for Therapeutic Radiology and Oncology (ASTRO) Meeting (served 1x)
- 2011: Moderator, Clinical Translation of Epigenetic in Cancer Therapy, San Diego, CA (served 1x)
- 2011-present: Reviewer, Nathan Schnaper Summer Intern Program candidates (1x annually)
- 2012: Co-Organizer and Moderator, 5th Annual Maryland Stem Cell Research Symposium, Annapolis, MD (served 1x)
- 2012: Speaker, Stem Cell Center Fund Raiser, Black Olive Inn, Maryland (served 1x)
- 2013: Moderator, Radiation Oncology Review Course, University of Maryland (served 1x)
- 2014: Coordinator, American Society of Hematology (ASH) Abstract Review, Category 601: Chromosomal Rearrangements and DNA Repair, San Francisco (served 1x)
- 2014: Moderator, Category 601: Chromosomal Rearrangements and DNA Repair. American Society of Hematology (ASH), San Francisco (served 1x)
- 2015: Chair, Minisymposia “Cancer Epigenetics”, American Association of Cancer Research (AACR) Annual Meeting, Philadelphia, PA (serve 1x)
- 2016: Chair: Special lecture, 18th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy, Houston Texas.
- 2017: Chair: DNA Repair Session, AACR New Frontiers in Cancer Research, Cape Town South Africa January 2017.
- 2016: Program Committee for the AACR New Frontiers in Cancer Research conference taking place January 18-22, 2017 in Cape Town, South Africa.
- 2016: AACR Regional Advisory Subcommittee on Africa.
- 2017: AACR-AstraZeneca Fellowship in Ovarian Cancer Research Committee
- DNA damage and repair assays
- Cell survival assays
- Clonogenic assays
- Molecular biology
- Western blotting
- Mouse xenograft studies in collaboration with Translational Core Facility UMGCCC
Tissue culture and cell storage: Four C02 incubators, three tissue culture hoods, two 40C refrigerators and two -200C freezers, Coulter cell counter (Z2), liquid nitrogen storage tank; Western blotting analysis: Gel electropheresis equipment (Biorad), including, power supplies (Biorad), Quantitative: End-point PCR machines, real-time PCR machines (Eppendorf), PCR hood, pipettes for PCR; DNA repair assays: bacterial incubator, fume hood, two gel imaging systems, nucleofector (Amaxa); General laboratory equipment: water baths, thermomixers and heat blocks, vortex apparatus, stir plates, hybridization chamber, 40C fridges, two -200C and two -800C freezers, pipetors, six microfuges centrifuges (at 40C and room temperature), three tabletop centrifuges, orbital shakers and rotators (for room temp and cold room reactions), macro- and microbalances, UV-visible spectrophotometer (Nanodrop and Nanovue), dissection, standard, and phase contrast microscopes, a Nikon micropht microscope with Nomarski optics, MJ thermal controller for PCR, fully automated HPLC, ELISA plate reader, cytospin centrifuge for immunofluorescence analysis of suspension cells, sample diluter/dispensers for RIA. Clonogenic Assays: A Synbiosis ProtoCOL3 colony counter. Shared departmental equipment includes standard and ultracentrifuges, a gamma-counter, liquid scintillation counter, microtome, spectrophotometer, cryostat, protein and nucleic acid electrophoresis and blotting system.
Other Shared Equipment:
The Radiation Oncology Research Laboratory is equipped with common equipment necessary for research including a Beckman Optima L-90k ultracentrifuge, a Beckman Avanti J-20XP centrifuge, a Beckman LS-6500 liquid scintillation counter, four large bacterial shakers, incubators for bacterial growth, Sonifier 250 (for ChIP studies), an Alpha-Innotech digital gel acquisition system, phosphoimager, 1 inverted fluorescent microscope, 1 standard Zeiss microscope, and a Zeiss and Nikon phase/brightfield/fluorescence microscope with an MC100 35mm camera, and a CCD digital camera, an X-ray machine, dark room with film processor, and a conference room are on site. In addition, there is joint use equipment located at the University of Maryland, Baltimore including a fluoroimager, dishwashing facilities, electron microscopy, confocal imaging center, mass spectroscopy, flowcytometry, the Center for Fluorescence Spectroscopy, Biopolymer Core Facility for sequencing and DNA Synthesis, and the MCB Freezer Program, an on-site biological reagent storehouse. Machine and electronic shops are available on a time/materials basis.