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Metastatic Bone Disease and IL-6 as Drivers of Cachexia in Kidney Cancer

Award Number: K08AR082457
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/07/2025
PERIOD OF PERFORMANCE END DATE: 04/30/2030

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Metastatic Bone Disease and IL-6 as Drivers of Cachexia in Kidney Cancer - PROJECT SUMMARY This proposal describes a five-year plan to develop Christopher Collier, MD into an independent orthopaedic- surgeon scientist whose career goal is to drive bench-to-bedside research that addresses the musculoskeletal effects of cancer. His prior education, research experience, and expertise in orthopaedic oncology prepare him for this opportunity. This career development award will catalyze his growth by providing complementary training in musculoskeletal biology, with an emphasis on muscle and bone biology, cancer cachexia, and laboratory leadership. Dr. Collier will receive exceptional mentorship and instruction at the Indiana University School of Medicine, an institution with a world-class environment for the study of musculoskeletal health and cancer. He will also benefit from strong institutional support, including independent laboratory space and protected research time, to enact his research plan. Cachexia is a syndrome of systemic muscle wasting and bone loss that is responsible for 20 to 40% of cancer-related deaths. Recent evidence suggests a direct link between cachexia and metastatic bone disease. The objective of this proposal, which addresses a critical need, is to define the contribution of metastatic bone disease to cachexia in kidney cancer and identify key mediators. Kidney cancer was selected because metastatic bone disease and cachexia are common disease features. Dr. Collier has established a mouse model of metastatic kidney cancer to bone, which develops cachexia and elevated serum IL-6. He hypothesizes that metastatic bone disease in kidney cancer increases systemic muscle wasting and bone loss by IL-6 mediated activation of JAK/STAT3 signaling in muscle. This hypothesis will be tested by pursuing three specific aims. Aim 1 will determine the impact of metastatic bone disease on cachexia in kidney cancer in vivo. Tumor cells will be implanted into mouse kidney, lung, or bone and cachexia outcomes compared. Aim 2 will determine the drivers of IL-6 signaling in kidney cancer and the potential of IL-6 blockade to reduce cachexia. IL-6 levels in serum and JAK/STAT3 signaling in muscle will be measured in tissues from Aim 1. IL-6 will also be deleted and/or pharmacologically neutralized in mice to determine the effect on cachexia. Finally, Aim 3 will establish the contribution of metastatic bone disease to cachexia and the IL-6 pathway in kidney cancer patients. Human serum and muscle will be collected from patients with localized kidney tumors or metastatic bone disease and compared. Collectively, these studies will describe the impact of metastatic bone disease and IL-6 on cachexia in kidney cancer. This research is conceptually innovative because it is the first to investigate the mechanisms of cachexia in metastatic kidney cancer and is technically innovative because it uses new preclinical models, a unique biorepository of human tissues, and cutting-edge approaches. This research is significant because it will likely provide strong scientific justification for or against new cachexia treatments targeting metastatic bone disease and the IL-6 pathway. It will also provide a pathway to scientific independence for a promising early-career orthopaedic-surgeon scientist.


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 = $156,210 )
2026	2026	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/24/2026	NON-COMPETING CONTINUATION	$156,210
														Subtotal = $156,210

Issue Date FY: 2025 ( Subtotal = $156,210 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/7/2025	NEW	$156,210
														Subtotal = $156,210

Grand Total All Awards = $312,420

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Metastatic Bone Disease and IL-6 as Drivers of Cachexia in Kidney Cancer

Award Number: K08AR082457

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/07/2025

PERIOD OF PERFORMANCE END DATE: 04/30/2030

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