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A New Target for Chromatin Remodeler Defects in Cancer

Award Number: R35CA231993
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2018
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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A New Target for Chromatin Remodeler Defects in Cancer - My laboratory has pioneered new research directions in environmental carcinogenesis for the past 25 years. We identified new targets for chemical carcinogens, new functions for “old” tumor suppressor genes, and elucidated the first mechanism by which environmental exposures during development could reprogram the epigenome to increase cancer risk in adulthood. It is my goal to continue to advance the field of cancer research by tackling challenging questions, rather than performing incremental research, which while safe, does little to “move the needle”. My objective for obtaining this R35 Outstanding Investigator Award is to focus my efforts on an exciting new discovery, which represents a paradigm shift in how we look at chromatin remodeler defects in cancer. As an unexpected off-shoot of our research on how environmental carcinogens reprogram the epigenome, we discovered a new function for the cell’s epigenetic machinery, and a new way for defects in chromatin remodeler genes to drive cancer. The Overarching Hypothesis for this R35 application is that the coding machinery known for “reading, writing and erasing” epigenetic methyl marks on chromatin plays a second, equally important but heretofore unappreciated, coding function “reading, writing and erasing” methyl marks on the cytoskeleton. We reported (Park et al Cell 2016), and support with additional Preliminary Data, that many chromatin remodelers are actually dual-function proteins, participating in both the Histone Code of chromatin, and the Tubulin Code of microtubules. This insight sets the stage for a new paradigm, wherein the cell’s methylation machinery serves two coding functions, one on chromatin and one on the cytoskeleton. It opens new frontiers for understanding how cells utilize and regulate one machinery with two distinct, but equally important coding functions. This is of special importance for cancer research, as we have been blind to the fact that defects in chromatin remodeler genes can directly impact the cytoskeleton, for example, via mitotic spindle defects that drive genomic instability and cytoskeletal defects that alter mobility to promote metastasis. The experiments proposed in this application are designed to open new doors for understanding the impact of chromatin remodeler defects in cancer, and for the development of therapies with efficacy against both the epigenetic and cytoskeletal alterations caused by defects in genes that encode dual-function chromatin-cytoskeleton remodelers.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	7	12/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $903,450 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	7	8/21/2024	NON-COMPETING CONTINUATION	$903,450
														Subtotal = $903,450

Issue Date FY: 2023 ( Subtotal = $931,976 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	6	8/21/2023	NON-COMPETING CONTINUATION	$931,976
														Subtotal = $931,976

Issue Date FY: 2022 ( Subtotal = $928,212 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	5	6/21/2022	NON-COMPETING CONTINUATION	$928,212
														Subtotal = $928,212

Issue Date FY: 2021 ( Subtotal = $950,996 )
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	4	7/16/2021	NON-COMPETING CONTINUATION	$950,996
														Subtotal = $950,996

Issue Date FY: 2020 ( Subtotal = $950,993 )
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	3	7/14/2020	NON-COMPETING CONTINUATION	$950,993
														Subtotal = $950,993

Issue Date FY: 2019 ( Subtotal = $922,470 )
2019	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	2	7/15/2019	NON-COMPETING CONTINUATION	$922,470
														Subtotal = $922,470

Issue Date FY: 2018 ( Subtotal = $594,375 )
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	1	7/31/2018	NEW	$594,375
														Subtotal = $594,375

Grand Total All Awards = $6,182,472

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A New Target for Chromatin Remodeler Defects in Cancer

Award Number: R35CA231993

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2018

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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