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Role of Macrophage Migration Inhibitory Factor (MIF) in KSHV-associated Malignancies

Award Number: R03DE034653
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Role of Macrophage Migration Inhibitory Factor (MIF) in KSHV-associated Malignancies - Kaposi’s Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s Sarcoma (KS) and Primary Effusion Lymphoma (PEL), which preferentially arise in immunocompromised patients (e.g., HIV+ personnel or organ transplant recipients) and lack of effective therapeutic options. Despite the reduced incidence of KS in the era of combined Antiretroviral Therapy (cART) for HIV infection, KS especially oral KS still remains one of the most common AIDS-associated tumors and a leading cause of morbidity and mortality in this setting. PEL is a rapidly progressing malignancy with a median survival time of approximately 6 months, even under the combinational chemotherapy. Macrophage migration inhibitory factor (MIF) signaling activation have been found closely related to many cancer cell malignant behaviors, however, its role in virus-associated cancers or how oncogenic viruses may regulate MIF signaling activities remain largely unknown. We recently found high levels of MIF signaling activities during KSHV infection or KSHV+ tumor cells in vitro and in vivo. Thus, we hypothesize that MIF signaling activation has important role in KSHV pathogenesis and oncogenesis, which may represent a promising direction to develop anticancer treatments for KSHV-related malignancies. To address this hypothesis, we propose the following Specific Aims: 1) To determine the underlying mechanisms of MIF signaling activation within KSHV+ tumor cells. 2) To develop MIF-targeted therapies against KSHV-related malignancies. Through these efforts, we hope to determine the roles of MIF signaling activation in KHSV pathogenesis and induced oncogenesis, and develop MIF signaling targeted therapies for improving the outcome of KSHV-related malignancies in high-risk immunocompromised patients.


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: 2025 ( Subtotal = $306,000 )
2025	2025	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Oral Diseases and Disorders Research	000	1	7/23/2025	NEW	$306,000
														Subtotal = $306,000

Grand Total All Awards = $306,000

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Role of Macrophage Migration Inhibitory Factor (MIF) in KSHV-associated Malignancies

Award Number: R03DE034653

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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