NIH R01 Grant for Glioblastoma Study and Translational Research

May 24, 2022

Baoli Hu, PhD, assistant professor of Neurological Surgery at UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh School of Medicine, was awarded a National Institutes of Health (NIH), National Cancer Institute R01 grant1 to further his research into the molecular mechanisms of glioblastoma immunosuppression and test a novel peptide developed and patented by Dr. Hu and colleagues in a combinatory approach with immune checkpoint inhibitors.

Dr. Hu's co-investigators include Carlos J. Camacho, PhD, associate professor in the Department of Computational and Systems Biology; Gary Kohanbash, PhD, assistant professor of Neurological Surgery; and Ian F. Pollack, MD, FACS, FAAP, Leland Albright Professor and Chief of Pediatric Neurosurgery at UPMC Children's.

Prior research2 by Dr. Hu and colleagues, published in the Journal of Clinical Investigation in July 2021, explored the showed how the glycoprotein complex chitinase-3-like 1 (CHI3L1) functions to suppress the immune system response in the tumor microenvironment of glioblastoma by recruiting and reprogramming tumor-associated macrophages to blunt T-cell activity allowing the tumors to grow and disseminate more easily. Additionally outlined in the paper, Dr. Hu's team developed and has since patented a novel peptide that has shown the ability to disrupt or knock down the CHI3L1 protein complexes' function and shrink tumors in preclinical studies.

Dr. Hu’s new R01 will significantly expand this line of research in an effort to develop a new therapeutic approach to combat glioblastomas.

"Developing new therapies is an urgent unmet need for patients with glioblastoma because current treatment options are usually ineffective and the tumors are often resistant, including immunotherapy that has been successful in other cancer types,” says Dr. Hu. “This new NIH grant will continue to support our research in developing potential drug candidates based on our recently defined cancer targets.”

The continuing investigation aims to further understand the mechanisms by which CHI3L1 recruits and reprograms tumor-associated macrophages to modulate immunosuppression in the tumor microenvironment and gather additional preclinical data on the use of immune checkpoint blockade through disrupting the CHI3L1 proteins.

Dr. Hu's study also has an important translational aspect. Using preclinical glioblastoma models, the team will use their novel peptide in combination with checkpoint inhibitors that target the PD-1, PD-L1, and CTLA4 pathways to gauge efficacy on slowing or reversing tumor growth and the impact on disease progression. 

Learn More About Dr. Hu and the Hu Laboratory.

References and Further Reading

1. Chitinase-3-Like-1 Mediated Immunosuppression in Glioblastoma. NIH Project Number: 1R01CA259124. Principal Investigator: Baoli Hu, PhD.

2. Chen A, Jiang Y, Li Z, Wu L, Santiago U, Zou H, Sharma V, Guan Y, McCarl LH, Ma J, Wu YL, Michel J, Shi Y, Konnikova L, Amankulor NM, Zinn PO, Kohanbash G, Agnihotri S, Lu S, Lu X, Sun D, Gittes GK, Wang Q, Xiao X, Yimlamai D, Pollack IF, Camacho CJ, Hu B. Chitinase-3-Like 1 Protein Complexes Modulate Macrophage-Mediated Immune Suppression in Glioblastoma. J Clin Invest. 2021 Aug 16; 131(16): e147552.