Rajasekaran Mahalingam
Department of Symptom Research, Division of Internal Medicine
About Rajasekaran Mahalingam
Dr. Raja Mahalingam holds a Ph.D. in structural biology and bioinformatics from National Tsing Hua University, Taiwan. In the early stages of his career, he delved into protein structure and dynamics under various disease conditions. However, his research trajectory eventually shifted towards transcriptomics analysis, with a focus on unraveling gene expression changes associated with disease.
In the Department of Symptom Research, Dr. Mahalingam is engaged in multiple projects. Notably, he discovered pivotal gene expression alterations in both neuronal and non-neuronal cells in mouse brains treated with doxorubicin. Also in a mouse model, he has revealed transcriptomic changes and identified crucial pathways that counter cisplatin-induced neurotoxicity. His work extends to neuropathic pain, where he has used RNA sequencing to showcase myeloid cell signatures and related pathways influencing inflammatory pain.
Given his keen interest in understanding the cellular mechanisms behind chemotherapy-induced cognitive impairment and neuropathy, Dr. Mahalingam employs bioinformatics approaches to elucidate key gene expression changes and cell type transformations. Additionally, he is interested in exploring metabolic shifts in chemotherapy-treated mouse brains and dorsal root ganglia, with the ultimate aim of identifying potential drug targets for these conditions.
Present Title & Affiliation
Primary Appointment
Assistant Professor, Department of Symptom Research CAO, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
Selected Publications
Peer-Reviewed Articles
- Robinson P, Italia Z, Italia Z, Hoang T, Rodriguez E, Eckols TK, Kasembeli M, Zorrilla LH, Soto LMS, Mahalingam R, Tweardy DJ. STAT3 Inhibition to Treat Ulcerative Colitis-Associated Colorectal Cancer. Int J Mol Sci 26(21), 2025. e-Pub 2025. PMID: 41226842.
- Martinez VK, McAlpin BR, Singh AK, Heijnen CJ, Mahalingam R. Single-Nucleus RNA Sequencing of HDAC6 Inhibition in Resolving Doxorubicin-Induced Cognitive Impairment. Mol Neurobiol 62(10):13557-13575, 2025. e-Pub 2025. PMID: 40542954.
- Nichols, JM, Pham, HV, Lee, E, Mahalingam, R, Shepherd, AJ. Single-cell analysis of age-related changes in leukocytes of diabetic mouse hindpaws. Cellular and Molecular Life Sciences 81(1), 2024. e-Pub 2024. PMID: 38502310.
- Garrity, R, Arora, N, Haque, MA, Weis, D, Trinh, RT, Neerukonda, SV, Kumari, S, Cortez, I, Ubogu, EE, Mahalingam, R, Tavares-Ferreira, D, Price, TJ, Kavelaars, A, Heijnen, CJ, Shepherd, AJ. Fibroblast-derived PI16 sustains inflammatory pain via regulation of CD206+ myeloid cells. Brain, behavior, and immunity 112:220-234, 2023. e-Pub 2023. PMID: 37315702.
- Milutinovic, B, Mahalingam, R, Mendt Vilchez, MC, Arroyo, LD, Seua, AV, Dharmaraj, S, Shpall, E, Heijnen, CJ. Intranasally Administered MSC-Derived Extracellular Vesicles Reverse Cisplatin-Induced Cognitive Impairment. International journal of molecular sciences 24(14), 2023. e-Pub 2023. PMID: 37511623.
- Khan S, Martinez-Ledesma E, Dong J, Mahalingam R, Park SY, Piao Y, Koul D, Balasubramaniyan V, de Groot JF, Yung WKA. Neuronal differentiation drives the antitumor activity of mitogen-activated protein kinase kinase (MEK) inhibition in glioblastoma. Neurooncol Adv 5(1):vdad132, 2023. e-Pub 2023. PMID: 38130900.
- Balogh M, Zhang J, Gaffney CM, Kalakuntla N, Nguyen NT, Trinh RT, Aguilar C, Pham HV, Milutinovic B, Nichols JM, Mahalingam R, Shepherd AJ. Sensory neuron dysfunction in orthotopic mouse models of colon cancer. J Neuroinflammation 19(1):204, 2022. e-Pub 2022. PMID: 35962398.
- Alexander, JF, Mahalingam, R, Seua, AV, Wu, S, Arroyo, LD, Hörbelt, T, Schedlowski, M, Blanco, E, Kavelaars, A, Heijnen, CJ. Targeting the Meningeal Compartment to Resolve Chemobrain and Neuropathy via Nasal Delivery of Functionalized Mitochondria. Advanced Healthcare Materials 11(8), 2022. e-Pub 2022. PMID: 35007407.
- Singh AK, Mahalingam R, Squillace S, Jacobson KA, Tosh DK, Dharmaraj S, Farr SA, Kavelaars A, Salvemini D, Heijnen CJ. Targeting the A(3) adenosine receptor to prevent and reverse chemotherapy-induced neurotoxicities in mice. Acta Neuropathol Commun 10(1):11, 2022. e-Pub 2022. PMID: 35093182.
- McAlpin BR, Mahalingam R, Singh AK, Dharmaraj S, Chrisikos TT, Boukelmoune N, Kavelaars A, Heijnen CJ. HDAC6 inhibition reverses long-term doxorubicin-induced cognitive dysfunction by restoring microglia homeostasis and synaptic integrity. Theranostics 12(2):603-619, 2022. e-Pub 2022. PMID: 34976203.
- Khan S, Mahalingam R, Sen S, Martinez-Ledesma E, Khan A, Gandy K, Lang FF, Sulman EP, Alfaro-Munoz KD, Majd NK, Balasubramaniyan V, de Groot JF. Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells. Cancers (Basel) 13(21), 2021. e-Pub 2021. PMID: 34771447.
- Mahalingam R, Dharmalingam P, Santhanam A, Kotla S, Davuluri G, Karmouty-Quintana H, Ashrith G, Thandavarayan RA. Single-cell RNA sequencing analysis of SARS-CoV-2 entry receptors in human organoids. J Cell Physiol 236(4):2950-2958, 2021. e-Pub 2021. PMID: 32944935.
- Chiang ACA, Seua AV, Singhmar P, Arroyo LD, Mahalingam R, Hu J, Kavelaars A, Heijnen CJ. Bexarotene normalizes chemotherapy-induced myelin decompaction and reverses cognitive and sensorimotor deficits in mice. Acta Neuropathol Commun 8(1):193, 2020. e-Pub 2020. PMID: 33183353.
- Rao W, Wang S, Duleba M, Niroula S, Goller K, Xie J, Mahalingam R, Neupane R, Liew AA, Vincent M, Okuda K, O'Neal WK, Boucher RC, Dickey BF, Wechsler ME, Ibrahim O, Engelhardt JF, Mertens TCJ, Wang W, Jyothula SSK, Crum CP, Karmouty-Quintana H, Parekh KR, Metersky ML, McKeon FD, Xian W. Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis. Cell 181(4):848-864.e18, 2020. e-Pub 2020. PMID: 32298651.
- Duleba M, Yamamoto Y, Neupane R, Rao W, Xie J, Qi Y, Liew AA, Niroula S, Zhang Y, Mahalingam R, Wang S, Goller K, Ajani JA, Vincent M, Ho KY, Hou JK, Hyams JS, Sylvester FA, Crum CP, McKeon F, Xian W. Cloning of ground-state intestinal stem cells from endoscopic biopsy samples. Nat Protoc 15(5):1612-1627, 2020. e-Pub 2020. PMID: 32238950.
- Duleba M, Mahalingam R, Liew AA, Qi Y, Neupane R, Vincent M, Agarwal S, Sylvester FA, Hyams JS, Ho KY, Hou JK, McKeon F, Xian W. Unlimited expansion of intestinal stem cells from a wide range of ages. Integr Mol Med 6(4), 2019. e-Pub 2019. PMID: 31463081.
- Duleba M, Qi Y, Mahalingam R, Liew AA, Neupane R, Flynn K, Rinaldi F, Vincent M, Crum CP, Ho KY, Hou JK, Hyams JS, Sylvester FA, McKeon F, Xian W. An Efficient Method for Cloning Gastrointestinal Stem Cells From Patients via Endoscopic Biopsies. Gastroenterology 156(1):20-23, 2019. e-Pub 2019. PMID: 30296437.
- Xian W, Duleba M, Qi Y, Mahalingam R, Vincent M, McKeon F. Ground-State Stem Cells: A Novel Approach for Adult Stem Cell Research. J Pediatr Pediatr Med 2(6):7-10, 2018. e-Pub 2018. PMID: 30957106.
- Mahalingam R, Peng HP, Yang AS. Prediction of fatty acid-binding residues on protein surfaces with three-dimensional probability distributions of interacting atoms. Biophys Chem 192:10-9, 2014. e-Pub 2014. PMID: 24934883.
- Mahalingam R, Peng HP, Yang AS. Prediction of FMN-binding residues with three-dimensional probability distributions of interacting atoms on protein surfaces. J Theor Biol 343:154-61, 2014. e-Pub 2014. PMID: 24211525.
- Luo SC, Lou YC, Rajasekaran M, Chang YW, Hsiao CD, Chen C. Structural basis of a physical blockage mechanism for the interaction of response regulator PmrA with connector protein PmrD from Klebsiella pneumoniae. J Biol Chem 288(35):25551-25561, 2013. e-Pub 2013. PMID: 23861396.
Review Articles
- Acharya, TK, Pan, Y, Grace, P, Heijnen, CJ, Mahalingam, R. Deciphering transcriptomic changes in chemobrain. Acta Neuropathologica Communications 13(1), 2025. e-Pub 2025. PMID: 40886025.
- Dharmalingam, P, Mahalingam, R, Yalamanchili, HK, Weng, T, Karmouty-Quintana, H, Guha, A, Thandavarayan, RA. Emerging roles of alternative cleavage and polyadenylation (APA) in human disease. Journal of Cellular Physiology 237(1):149-160, 2022. e-Pub 2022. PMID: 34378793.
Patient Reviews
CV information above last modified March 25, 2026