Wednesday, December 17, 2025 12/17/2025

Biological Indicators of Racial Disparity in Ameloblastoma Recurrence

Award Number: R01CA259307
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/14/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

View Award Description

Biological Indicators of Racial Disparity in Ameloblastoma Recurrence - Project Summary Ameloblastoma accounts for 14% of all odontogenic tumors and African-Americans are five times more likely to develop ameloblastoma compared to Caucasians. Despite radical surgery, 10% of ameloblastomas recur and 25% of recurrent ameloblastomas occur in the black racial group. The biological determinants of ameloblastoma racial disparity are unclear and there are no specific biological markers to predict recurrence. Most ameloblastomas display genetic mutations of BRAF that encodes the serine/threonine protein kinase B-Raf, an activator of MAPK/ERK-signaling pathway. BRAF oncogenes induce the expression of key autophagic markers that include LC3, p62 and BECLIN1. High expressions of p62, ATG7 and LC3 have been identified in all variants of ameloblastoma and our in vivo mouse ameloblastoma tumor model displayed elevated LC3 and p62 levels. These suggest ameloblastoma recurrence can be attributed to autophagic cell survival mechanisms of residual invasive neoplastic odontogenic epithelium. Interplay of autophagic regulator BECNLIN1 with RUBICON [Run domain Beclin-1-interacting and cysteine-rich domain-containing protein], a component of LC3-associated phagocytosis (LAP) dysregulates autophagosomal maturation and endocytic trafficking to promote tumor migration and invasiveness. Our hypothesis is that autophagy reactivates residual invasive odontogenic epithelium by LAP-mediated entosis and recycling of bioenergetic cellular components. Our collaborative group has a relatively large cohort of ameloblastoma tissues and have generated epithelial-derived (EP-AMCs) and mesenchymal-derived (MS-AMCs) ameloblastoma cell lines from BRAF V600E+ multicystic/follicular ameloblastomas. To elucidate biological mechanisms contributing to racial disparity in Black versus White racial groups, we will determine prognostic biomarkers of ameloblastoma recurrence and assess how LC3-mediated autophagic ‘cargo’ processing orchestrate recurrence disparity. In Aim 1 we will determine whether autophagic proteins are pro-oncogenic adaptors associated with ameloblastoma racial disparity, aggressive phenotype and propensity for recurrence. In Aim 2, we will assess whether residual invasive ameloblastic epithelium survive using LAP-mediated entosis and recycling of bioenergetic cellular components. While ameloblastoma is relatively rare, understanding the interplay of two converging cytoprotective pathways in ameloblastoma growth pattern and recurrence has the potential to lead to new prognostic biomarkers and precision-guided therapies to alleviate racial disparities in BRAF+ tumors like ameloblastoma.


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 = $334,547 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	5	12/10/2025	NON-COMPETING CONTINUATION	$334,547
														Subtotal = $334,547

Issue Date FY: 2025 ( Subtotal = $371,719 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	4	11/26/2024	NON-COMPETING CONTINUATION	$334,547
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	001	4	6/2/2025	NON-COMPETING CONTINUATION	$37,172
														Subtotal = $371,719

Issue Date FY: 2024 ( Subtotal = $353,134 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	3	12/1/2023	NON-COMPETING CONTINUATION	$334,547
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	001	3	4/18/2024	NON-COMPETING CONTINUATION	$18,587
														Subtotal = $353,134

Issue Date FY: 2023 ( Subtotal = $364,284 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	2	12/20/2022	NON-COMPETING CONTINUATION	$334,547
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	001	2	3/16/2023	NON-COMPETING CONTINUATION	$29,737
														Subtotal = $364,284

Issue Date FY: 2022 ( Subtotal = $371,719 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	1	12/14/2021	NEW	$371,719
														Subtotal = $371,719

Grand Total All Awards = $1,795,403

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Biological Indicators of Racial Disparity in Ameloblastoma Recurrence

Award Number: R01CA259307

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/14/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer