Bhutiani Lab

About

The Bhutiani lab focuses on the mechanistic underpinnings driving differential treatment response and overcome resistance to immune-based therapies and cytotoxic chemotherapy among patients with colorectal malignancies. Colon and rectal cancer is the third most common cancer globally and results in over 900,000 deaths worldwide. Despite the promise of immunotherapy for colorectal cancer, only a small fraction (~10%) of patients respond to immune based therapies. The lab is actively exploring how interactions between immune cells in the local microenvironment affects immunotherapy response and how exploiting those interactions can improve immunotherapy efficacy in colorectal cancer patients. We also investigate how immune populations, circulating metabolites, gut microbes, and epithelial integrity impact conventional systemic therapy and immunotherapy efficacy as well as the potential of novel biologic agents to treat colorectal cancer. We utilize numerous techniques for these investigations, including in vitro cell culture experiments, multiple in vivo animal models, patient samples, spatial imaging, bulk and single cell RNA sequencing, and microbiome and metabolomic analyses. The lab helps oversee and has access to a biorepository of longitudinally collected blood, stool, and tissue from patients undergoing treatment for colorectal cancer, enhancing translational capacity of our research efforts to improve care and clinical outcomes for colorectal cancer patients.

Key Research Areas

• Mechanisms of lack of efficacy of immunotherapy in microsatellite stable/mismatch repair proficient colon and rectal cancer
• nAssessment of novel immune-based therapies for primary and metastatic colorectal cancer
• nHigh-fidelity preclinical models of primary and metastatic colon and rectal cancer
• Influence of microbes and metabolites on immune cell polarization/phenotype and treatment activity in setting of malignancy

Current Projects

• Delineation and modulation of T cell-neutrophil interactions in determining immunotherapy response in primary and metastatic colorectal cancer
• nMacrophage modulation to improve treatment response in colorectal peritoneal metastases
• Identifying interactions among disease sites (primary tumor, lymph node, liver), specifically with respect to immune phenotype and modulation of treatment response, along the pathway of metastatic progression in colorectal cancer.
• Ex vivo assessment of multispecific T cell-DC engagers in solid tumors

Team

• Neal Bhutiani, MD, PhD, Principal Investigator (neal.bhutiani@louisville.edu)
• Kamila Bujko, PhD, Research Scientist and Lab Manager (kamila.bujko@louisville.edu)
• Trinity Marlar, MS, Research Technician (trinity.marlar@louisville.edu)

Recent Publications

• Bhutiani N, Li Q, Anderson CD, Gallagher HC, De Jesus M, Singh R, Jala VR, Fraig M, Gu T, Egilmez NK. Enhanced gut barrier integrity sensitizes colon cancer to immune therapy. Oncoimmunology. 2018 Aug 23;7(11):e1498438. PMID: 30377564
• Bhutiani N, Grizzle WE, Galandiuk S, Otali D, Dryden GW, Egilmez NK, McNally LR. Noninvasive Imaging of Colitis Using Multispectral Optoacoustic Tomography. J Nucl Med. 2017 Jun;58(6):1009-1012. PMID: 27908970
• Bhutiani N, Samykutty A, McMasters KM, Egilmez NK, McNally LR. In vivo tracking of orally-administered particles within the gastrointestinal tract of murine models using multispectral optoacoustic tomography. Photoacoustics. 2018 Nov 17;13:46-52. PMID: 30555786
• Bhutiani N, Wargo JA. Gut microbes as biomarkers of ICI response - sharpening the focus. Nat Rev Clin Oncol. 2022 Aug;19(8):495-496. PMID: 35449306
• Park EM, Chelvanambi M, Bhutiani N, Kroemer G, Zitvogel L, Wargo JA. Targeting the gut and tumor microbiota in cancer. Nat Med. 2022 Apr;28(4):690-703. PMID: 3544072
• Mandal RK, Denny JE, Waide ML, Li Q, Bhutiani N, Anderson CD, Baby BV, Jala VR, Egilmez NK, Schmidt NW. Temporospatial shifts within commercial laboratory mouse gut microbiota impact experimental reproducibility. BMC Biol. 2020 Jul 3;18(1):83. PMID: 32620114
• Bhutiani N, et al. Assessing Disease Control in Mismatch Repair-Proficient Colorectal Cancer With Peritoneal Metastases Treated With Immune Checkpoint Blockade-Based Combination Therapies. JCO Oncol Adv 1, e2400018(2024).