Dr. MANISH CHARAN
 
 
First Name
MANISH
Last Name
CHARAN
University/Institution
The Ohio state university
Email ID
charanmanish@gmail.com
City
Columbus
Country
United States
State
Ohio
Zip code
43215
Department
Area of Research
Tumor microenvironment and Immunotherapy
Area of Expertise
Tumor Biology
Brief Description of Research Interest:
 

Having received my early scientifictraining in applied science, my focus in research has consistently beenoriented towards translation. Throughout my PhD and Post-doctoral experience inIndia and the United States, I was in a unique position to partake in and learnfrom both basic as well as clinical and intervention based research. During my pre-doctoral research at CSIR-Central DrugResearch Institute India, my work was focused on the biology of a deadliestmalarial parasite: Plasmodium falciparum.I was able to elucidate the indispensable iron-sulfur cluster biogenesis pathwayin the apicoplast via SUF pathway. My work has provided the firstexperimental evidence for an active SUF machinery in the Plasmodium apicoplast, a pathway that is absent in humans and thusoffers a unique site for drug intervention and discovery efforts.

 

Next, I moved to United States as apostdoctoral scientist at Nationwide Children’s Hospital. Here, my study wasfocused on understanding the role of oncogenic p53 family members in thegenesis of pediatric sarcomas, and developing approaches to inhibit thesesignaling pathways. We have demonstrated that ΔNp63 (p63-isoform) is associatedwith metastatic behavior in osteosarcoma. Our studies revealed that inhibition ofΔNp63 by nanoparticles sensitizes osteosarcoma tumors to doxorubicin treatment.In another study, my research work on ΔNp73 (p73-isoform), demonstrated that itpromotes glioblastoma pathogenesis by interacting with ETS2 protein. This workprovided the first experimental evidence that ΔNp73-ETS2 complex directlyactivates both Ang1 and Tie2 gene expression in tumor cells. Furthermore, Iworked on Δ133p53: a p53 isoform and discovered that Δ133p53 induces HGFsecretion and regulates Ewing sarcoma growth and metastasis. In addition, wefound that HGF receptor-neutralizing antibody (AMG102) in combination with GD2-specific;CAR-reengineered T-cell therapy synergistically inhibited primary tumor growthand metastatic spread using preclinical animal models. Furthermore, I wasable to determine the role of apro-inflammatory molecule: macrophage migration inhibitory factor (MIF)and established its role in triple-negative breast cancer (TNBC) progressionand metastasis. In addition, I have identified a novelMIF-specific chemical inhibitor, CPSI-1306 that inhibits TNBC growth andmetastasis.

 

My currentresearch interests include elucidating novel signaling pathways that regulate tumor growth, metastasis,and drug resistance in cancers and developing innovative immune-based therapiesfor solid tumors especially for small cell lung cancer and triple-negativebreast cancer.  

 
Representative Publications:
 
1. Charan M, Das S, Mishra S, Chatterjee N, Varikuti S, Kaul K, et al. Macrophage migration inhibitory factor inhibition as a novel therapeutic approach against triple-negative breast cancer. Cell Death Dis. 2020;11(9):774.

2. Charan M, Verma AK, Hussain S, Misri S, Mishra S, Majumder S, et al. Molecular and Cellular Factors Associated with Racial Disparity in Breast Cancer. Int J Mol Sci. 2020;21(16).

3. #Cam M, #Charan M, #Welker AM, Dravid P, Studebaker AW, Leonard JR, et al. DeltaNp73/ETS2 complex drives glioblastoma pathogenesis- targeting downstream mediators by rebastinib prolongs survival in preclinical models of glioblastoma. (# equally contributed author).Neuro Oncol. 2020;22(3):345-56.

4. Charan M, Dravid P, Cam M, Setty B, Roberts RD, Houghton PJ, et al. Tumor secreted ANGPTL2 facilitates recruitment of neutrophils to the lung to promote lung pre-metastatic niche formation and targeting ANGPTL2 signaling affects metastatic disease. Oncotarget. 2020;11(5):510-22.

5. Charan M, Dravid P, Cam M, Audino A, Gross AC, Arnold MA, et al. GD2-directed CAR-T cells in combination with HGF-targeted neutralizing antibody (AMG102) prevent primary tumor growth and metastasis in Ewing sarcoma. Int J Cancer. 2020;146(11):3184-95.

6. #Charan M, Kushwaha B, Mishra S, and Ganju RK. Epithelial-Mesenchymal Transition (EMT) in Breast Cancer: An Overview. Current Advances in Breast Cancer Research: A Molecular Approach. ISBN: 978-981-14-5142-3. Bentham science publishers (2020). (# Corresponding author).

7. Mishra S, Charan M, Misri S, Ahirwar D, Ganju RK. miRNA Biology in Breast Cancer Progression. In: Suman S, Suman G, Mishra S, editors. Current advances in breast cancer research: A molecular approach. Bentham science publishers; 2020. p. 254–277.

8. Das S, Kaul K, Mishra S, Charan M, Ganju RK. Cannabinoid Signaling in Cancer. Adv Exp Med Biol. 2019;1162:51-61.

9. Charan M, Choudhary HH, Singh N, Sadik M, Siddiqi MI, Mishra S, et al. [Fe-S] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite. FEBS J. 2017;284(16):2629-48.

10. Charan M and Habib S. Biosynthesis of [Fe-S] proteins in the apicoplast. (2015). Encyclopedia of Malaria (Springer). DOI 10.1007/978-1-4614-8757-9_44-2.

11. Charan M, Singh N, Kumar B, Srivastava K, Siddiqi MI, Habib S. Sulfur mobilization for Fe-S cluster assembly by the essential SUF pathway in the Plasmodium falciparum apicoplast and its inhibition. Antimicrob Agents Chemother. 2014;58(6):3389-98.

12. Kumar B, Chaubey S, Shah P, Tanveer A, Charan M, Siddiqi MI, et al. Interaction between sulphur mobilisation proteins SufB and SufC: evidence for an iron-sulphur cluster biogenesis pathway in the apicoplast of Plasmodium falciparum. Int J Parasitol. 2011;41(9):991-9.

13. Tanveer A, Allen SM, Jackson KE, Charan M, Ralph SA, Habib S. An FtsH protease is recruited to the mitochondrion of Plasmodium falciparum. PLoS One. 2013;8(9):e74408.