Professional Summary
Leads a multidisciplinary team of investigators focused on developing target and mechanism specific modulators of disease relevant targets. Brings > 20 years of experience in all aspects of drug discovery. Advanced multiple compounds through preclinical studies that include ADMET and PD studies. Authored > 100 peer-reviewed scientific publications and continuously supported as PI on NIH grants for nearly 2-decades. Served on numerous review panels for various funding organizations, including as a permanent member on the NIH drug discovery and molecular pharmacology (DMP) study section. Mentored to completion 9 Ph.D. students, 5 M.S. students, 22 postdoctoral associates and 7 junior faculty. Students and postdoctoral fellows have successfully transitioned to independent positions in academia and industry.
Education
BS: Madras Christian College Madras, India, 1994 (Chemistry)
MS: Indian Institute of Technology Madras, India, 1996 (Chemistry)
PhD: University of Vermont Burlington, VT, 2001 (Organic Chemistry)
Positions and Work Experience
04-01-2001 -04-30-2005 Postdoctoral Research Associate, Harvard Medical School, Boston, MA. "Developed small molecule translation initiation inhibitors for cancer therapy."
05-01-2005 -06-30-2009 Assistant Professor, University of Texas Medical Branch, Galveston, TX. "Established a research program focused on developing small molecule inhibitors of protein-protein interactions"
07-01-2009 -06-30-2014 Associate Professor, University of Nebraska Medical Center, Omaha, NE. "Expanded the research program to include targeting disease relevant proteins implicated in cancer"
07-01-2014 -07-31-2025 Professor, University of Nebraska Medical Center, Omaha, NE. "Led multidisciplinary drug discovery teams to advance compounds through preclinical development"
08-01-2017 -07-30-2024 Program Leader, Fred & Pamela Buffett Cancer Center, Omaha, NE. "Targets Modulators and Delivery"
07-01-2021 -07-31-2025 Ruth Branham Professor, University of Nebraska Medical Center, Omaha, NE. "Expanded the scope of the research program to include covalent modulators and heterobifunctional compounds (PROTACs & RIPTACs)"
06-01-2023 -05-30-2024 President, Faculty Senate, University of Nebraska Medical Center, Omaha, NE
08-01-2025 - James L. Winkle Chair, University of Cincinnati, Cincinnati, OH
Publications
Peer Reviewed Publications
Boghean, Lidia; Singh, Sarbjit; Mangalaparthi, Kiran K; Kizhake, Smitha; Umeta, Lelisse; Wishka, Donn; Grothaus, Paul; Pandey, Akhilesh; Natarajan, Amarnath (2025. ) A Selective MAP3K1 Inhibitor Facilitates Discovery of NPM1 as a Member of the Network.Molecules (Basel, Switzerland), , 30 (9 ) , More Information
Mallareddy, Jayapal Reddy; Yang, Lin; Lin, Wan-Hsin; Feathers, Ryan; Ayers-Ringler, Jennifer; Tolosa, Ezequiel; Kizhake, Amritha G; Kizhake, Smitha; Kubica, Sydney P; Boghean, Lidia; Alvarez, Sophie; Naldrett, Michael J; Singh, Sarbjit; Rana, Sandeep; Zahid, Muhammad; Schaefer-Klein, Janet; Roden, Anja; Kosari, Farhad; Anastasiadis, Panos Z; Borad, Mitesh; Natarajan, Amarnath; Mansfield, Aaron S (2025. ) Fluorescence based live cell imaging identifies exon 14 skipped hepatocyte growth factor receptor (MET) degraders.RSC advances, , 15 (13 ) ,10419-10425 More Information
Azadmanesh, Jahaun; Slobodnik, Katelyn; Struble, Lucas R; Lovelace, Jeffrey J; Cone, Erika A; Dasgupta, Medhanjali; Lutz, William E; Kumar, Siddhartha; Natarajan, Amarnath; Coates, Leighton; Weiss, Kevin L; Myles, Dean A A; Kroll, Thomas; Borgstahl, Gloria E O (2025. ) The role of Tyr34 in proton coupled electron transfer and product inhibition of manganese superoxide dismutase.Nature communications, , 16 (1 ) ,1887 More Information
Tolosa, Ezequiel J; Yang, Lin; Ayers-Ringler, Jennifer; Suzuki, Shinichiro; Mallareddy, Jayapal Reddy; Schaefer-Klein, Janet; Borad, Mitesh; Kosari, Farhad; Natarajan, Amarnath; Mansfield, Aaron S (2024. ) Proteolysis targeting chimera (PROTAC)-driven antibody internalization of oncogenic cell surface receptors.Communications biology, , 7 (1 ) ,1719 More Information
Mukthapuram, Prathap Reddy; Natarajan, Amarnath (2024. ) Domino Reactions Enable Zn-Mediated Direct Synthesis of Spiro-Fused 2-Oxindole-α-Methylene-γ-Butyrolactones/Lactams from Isatin Derivatives and 2-(Bromomethyl)acrylates.Molecules (Basel, Switzerland), , 29 (15 ) , More Information
Eiken, Alexandria P; Smith, Audrey L; Skupa, Sydney A; Schmitz, Elizabeth; Rana, Sandeep; Singh, Sarbjit; Kumar, Siddhartha; Mallareddy, Jayapal Reddy; de Cubas, Aguirre A; Krishna, Akshay; Kalluchi, Achyuth; Rowley, M Jordan; D'Angelo, Christopher R; Lunning, Matthew A; Bociek, R Gregory; Vose, Julie M; Natarajan, Amarnath; El-Gamal, Dalia (2024. ) Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects.Cancer research communications, , 4 (5 ) ,1328-1343 More Information
Murthy, Divya; Attri, Kuldeep S; Shukla, Surendra K; Thakur, Ravi; Chaika, Nina V; He, Chunbo; Wang, Dezhen; Jha, Kanupriya; Dasgupta, Aneesha; King, Ryan J; Mulder, Scott E; Souchek, Joshua; Gebregiworgis, Teklab; Rai, Vikant; Patel, Rohit; Hu, Tuo; Rana, Sandeep; Kollala, Sai Sundeep; Pacheco, Camila; Grandgenett, Paul M; Yu, Fang; Kumar, Vikas; Lazenby, Audrey J; Black, Adrian R; Ulhannan, Susanna; Jain, Ajay; Edil, Barish H; Klinkebiel, David L; Powers, Robert; Natarajan, Amarnath; Hollingsworth, Michael A; Mehla, Kamiya; Ly, Quan; Chaudhary, Sarika; Hwang, Rosa F; Wellen, Kathryn E; Singh, Pankaj K (2024. ) Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis.Nature cell biology, , 26 (4 ) ,613-627 More Information
Wallin, Savanna; Singh, Sarbjit; Borgstahl, Gloria E O; Natarajan, Amarnath (2023. ) Design, synthesis, and evaluation of a mitoxantrone probe (MXP) for biological studies.Bioorganic & medicinal chemistry letters, , 94 ,129465 More Information
Gupta, Priyanka; Strange, Keehn; Telange, Rahul; Guo, Ailan; Hatch, Heather; Sobh, Amin; Elie, Jonathan; Carter, Angela M; Totenhagen, John; Tan, Chunfeng; Sonawane, Yogesh A; Neuzil, Jiri; Natarajan, Amarnath; Ovens, Ashley J; Oakhill, Jonathan S; Wiederhold, Thorsten; Pacak, Karel; Ghayee, Hans K; Meijer, Laurent; Reddy, Sushanth; Bibb, James A (2022. ) Genetic impairment of succinate metabolism disrupts bioenergetic sensing in adrenal neuroendocrine cancer.Cell reports, , 40 (7 ) ,111218 More Information
Rana, Sandeep; Kour, Smit; Kizhake, Smitha; King, Hannah M; Mallareddy, Jayapal Reddy; Case, Adam J; Huxford, Tom; Natarajan, Amarnath (2022. ) Dimers of isatin derived α-methylene-γ-butyrolactone as potent anti-cancer agents.Bioorganic & medicinal chemistry letters, , 65 ,128713 More Information
Napoleon, John Victor; Sagar, Satish; Kubica, Sydney P; Boghean, Lidia; Kour, Smit; King, Hannah M; Sonawane, Yogesh A; Crawford, Ayrianne J; Gautam, Nagsen; Kizhake, Smitha; Bialk, Pawel A; Kmiec, Eric; Mallareddy, Jayapal Reddy; Patil, Prathamesh P; Rana, Sandeep; Singh, Sarbjit; Prahlad, Janani; Grandgenett, Paul M; Borgstahl, Gloria E O; Ghosal, Gargi; Alnouti, Yazen; Hollingsworth, Michael A; Radhakrishnan, Prakash; Natarajan, Amarnath (2022. ) Small-molecule IKKβ activation modulator (IKAM) targets MAP3K1 and inhibits pancreatic tumor growth.Proceedings of the National Academy of Sciences of the United States of America, , 119 (18 ) ,e2115071119 More Information
Kour, Smit; Rana, Sandeep; Kubica, Sydney P; Kizhake, Smitha; Ahmad, Mudassier; Muñoz-Trujillo, Catalina; Klinkebiel, David; Singh, Sarbjit; Mallareddy, Jayapal Reddy; Chandra, Surabhi; Woods, Nicholas T; Karpf, Adam R; Natarajan, Amarnath (2022. ) Spirocyclic dimer SpiD7 activates the unfolded protein response to selectively inhibit growth and induce apoptosis of cancer cells.The Journal of biological chemistry, , 298 (5 ) ,101890 More Information
Kour, Smit; Rana, Sandeep; Kizhake, Smitha; Lagundžin, Dragana; Klinkebiel, David; Mallareddy, Jayapal Reddy; Huxford, Tom; Woods, Nicholas T; Natarajan, Amarnath (2022. ) Stapling proteins in the RELA complex inhibits TNFα-induced nuclear translocation of RELA.RSC chemical biology, , 3 (1 ) ,32-36 More Information
Mallareddy, Jayapal Reddy; Singh, Sarbjit; Boghean, Lidia; Natarajan, Amarnath (2022. ) Selective CDK9 degradation using a proteolysis-targeting chimera (PROTAC) strategy.Future medicinal chemistry, , 14 (3 ) ,131-134 More Information
Rana, Sandeep; Mallareddy, Jayapal Reddy; Singh, Sarbjit; Boghean, Lidia; Natarajan, Amarnath (2021. ) Inhibitors, PROTACs and Molecular Glues as Diverse Therapeutic Modalities to Target Cyclin-Dependent Kinase.Cancers, , 13 (21 ) , More Information
Sagar, Satish; Singh, Sarbjit; Mallareddy, Jayapal Reddy; Sonawane, Yogesh A; Napoleon, John V; Rana, Sandeep; Contreras, Jacob I; Rajesh, Christabelle; Ezell, Edward L; Kizhake, Smitha; Garrison, Jered C; Radhakrishnan, Prakash; Natarajan, Amarnath (2021. ) Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy.European journal of medicinal chemistry, , 222 ,113579 More Information
King, Hannah M; Rana, Sandeep; Kubica, Sydney P; Mallareddy, Jayapal Reddy; Kizhake, Smitha; Ezell, Edward L; Zahid, Muhammad; Naldrett, Michael J; Alvarez, Sophie; Law, Henry C-H; Woods, Nicholas T; Natarajan, Amarnath (2021. ) Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax.Bioorganic & medicinal chemistry letters, , 43 ,128061 More Information
Napoleon, John V; Singh, Sarbjit; Rana, Sandeep; Bendjennat, Mourad; Kumar, Vikas; Kizhake, Smitha; Palermo, Nicholas Y; Ouellette, Michel M; Huxford, Tom; Natarajan, Amarnath (2021. ) Small molecule binding to inhibitor of nuclear factor kappa-B kinase subunit beta in an ATP non-competitive manner.Chemical communications (Cambridge, England), , 57 (38 ) ,4678-4681 More Information
Rana, Sandeep; Natarajan, Amarnath (2021. ) Small molecule induced polymerization of BCL6 facilitates SIAH1 mediated degradation.Signal transduction and targeted therapy, , 6 (1 ) ,142 More Information
Rana, Sandeep; Kour, Smit; Sonawane, Yogesh A; Robb, Caroline M; Contreras, Jacob I; Kizhake, Smitha; Zahid, Muhammad; Karpf, Adam R; Natarajan, Amarnath (2020. ) Symbiotic prodrugs (SymProDs) dual targeting of NFkappaB and CDK.Chemical biology & drug design, , 96 (2 ) ,773-784 More Information
Kour, Smit; Rana, Sandeep; Contreras, Jacob I; King, Hannah M; Robb, Caroline M; Sonawane, Yogesh A; Bendjennat, Mourad; Crawford, Ayrianne J; Barger, Carter J; Kizhake, Smitha; Luo, Xu; Hollingsworth, Michael A; Natarajan, Amarnath (2019. ) CDK5 Inhibitor Downregulates Mcl-1 and Sensitizes Pancreatic Cancer Cell Lines to Navitoclax.Molecular pharmacology, , 96 (4 ) ,419-429 More Information
Nowialis, Pawel; Lopusna, Katarina; Opavska, Jana; Haney, Staci L; Abraham, Ajay; Sheng, Peike; Riva, Alberto; Natarajan, Amarnath; Guryanova, Olga; Simpson, Melanie; Hlady, Ryan; Xie, Mingyi; Opavsky, Rene (2019. ) Catalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions.Nature communications, , 10 (1 ) ,4374 More Information
Zheng, Xiao-Feng; Acharya, Sanket S; Choe, Katherine N; Nikhil, Kumar; Adelmant, Guillaume; Satapathy, Shakti Ranjan; Sharma, Samanta; Viccaro, Keith; Rana, Sandeep; Natarajan, Amarnath; Sicinski, Peter; Marto, Jarrod A; Shah, Kavita; Chowdhury, Dipanjan (2019. ) A mitotic CDK5-PP4 phospho-signaling cascade primes 53BP1 for DNA repair in G1.Nature communications, , 10 (1 ) ,4252 More Information
Rana, Sandeep; Bendjennat, Mourad; Kour, Smit; King, Hannah M; Kizhake, Smitha; Zahid, Muhammad; Natarajan, Amarnath (2019. ) Selective degradation of CDK6 by a palbociclib based PROTAC.Bioorganic & medicinal chemistry letters, , 29 (11 ) ,1375-1379 More Information
Contreras, Jacob I; Robb, Caroline M; King, Hannah M; Baxter, Jared; Crawford, Ayrianne J; Kour, Smit; Kizhake, Smitha; Sonawane, Yogesh A; Rana, Sandeep; Hollingsworth, Michael A; Luo, Xu; Natarajan, Amarnath (2018. ) Chemical Genetic Screens Identify Kinase Inhibitor Combinations that Target Anti-Apoptotic Proteins for Cancer Therapy.ACS chemical biology, , 13 (5 ) ,1148-1152 More Information
Naramura, Mayumi; Natarajan, Amarnath (2018. ) Mouse Pancreatic Tumor Model Independent of Tumor Suppressor Gene Inactivation.Pancreas, , 47 (5 ) ,e27-e29 More Information
Sonawane, Yogesh A; Zhu, Yingmin; Garrison, Jered C; Ezell, Edward L; Zahid, Muhammad; Cheng, Xiaodong; Natarajan, Amarnath (2017. ) Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors.ACS medicinal chemistry letters, , 8 (11 ) ,1183-1187 More Information
Robb, Caroline M; Contreras, Jacob I; Kour, Smit; Taylor, Margaret A; Abid, Mohammad; Sonawane, Yogesh A; Zahid, Muhammad; Murry, Daryl J; Natarajan, Amarnath; Rana, Sandeep (2017. ) Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC).Chemical communications (Cambridge, England), , 53 (54 ) ,7577-7580 More Information
Arnst, Jamie L; Hein, Ashley L; Taylor, Margaret A; Palermo, Nick Y; Contreras, Jacob I; Sonawane, Yogesh A; Wahl, Andrew O; Ouellette, Michel M; Natarajan, Amarnath; Yan, Ying (2017. ) Discovery and characterization of small molecule Rac1 inhibitors.Oncotarget, , 8 (21 ) ,34586-34600 More Information
Abid, Mohammad; Sonawane, Yogesh A; Contreras, Jacob I; Rana, Sandeep; Natarajan, Amarnath (2017. ) Recent Advances in Cancer Drug Development: Targeting Induced Myeloid Cell Leukemia-1 (Mcl-1) Differentiation Protein.Current medicinal chemistry, , 24 (40 ) ,4488-4514 More Information
Sonawane, Yogesh A; Taylor, Margaret A; Napoleon, John Victor; Rana, Sandeep; Contreras, Jacob I; Natarajan, Amarnath (2016. ) Cyclin Dependent Kinase 9 Inhibitors for Cancer Therapy.Journal of medicinal chemistry, , 59 (19 ) ,8667-8684 More Information
Rana, Sandeep; Blowers, Elizabeth C; Tebbe, Calvin; Contreras, Jacob I; Radhakrishnan, Prakash; Kizhake, Smitha; Zhou, Tian; Rajule, Rajkumar N; Arnst, Jamie L; Munkarah, Adnan R; Rattan, Ramandeep; Natarajan, Amarnath (2016. ) Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.Journal of medicinal chemistry, , 59 (10 ) ,5121-7 More Information
Rana, Sandeep; Blowers, Elizabeth C; Natarajan, Amarnath (2015. ) Small molecule adenosine 5'-monophosphate activated protein kinase (AMPK) modulators and human diseases.Journal of medicinal chemistry, , 58 (1 ) ,2-29 More Information
Arnst, Jamie L; Davies, Christopher W; Raja, Srikumar M; Das, Chittaranjan; Natarajan, Amarnath (2013. ) High-throughput compatible fluorescence resonance energy transfer-based assay to identify small molecule inhibitors of AMSH deubiquitinase activity.Analytical biochemistry, , 440 (1 ) ,71-7 More Information
Radhakrishnan, Prakash; Bryant, Vashti C; Blowers, Elizabeth C; Rajule, Rajkumar N; Gautam, Nagsen; Anwar, Muhammad M; Mohr, Ashley M; Grandgenett, Paul M; Bunt, Stephanie K; Arnst, Jamie L; Lele, Subodh M; Alnouti, Yazen; Hollingsworth, Michael A; Natarajan, Amarnath (2013. ) Targeting the NF-κB and mTOR pathways with a quinoxaline urea analog that inhibits IKKβ for pancreas cancer therapy.Clinical cancer research : an official journal of the American Association for Cancer Research, , 19 (8 ) ,2025-35 More Information
Rana, Sandeep; Natarajan, Amarnath (2013. ) Face selective reduction of the exocyclic double bond in isatin derived spirocyclic lactones.Organic & biomolecular chemistry, , 11 (2 ) ,244-7 More Information
Kumar, Eric A; Chen, Qianyi; Kizhake, Smitha; Kolar, Carol; Kang, Myungshim; Chang, Chia-En A; Borgstahl, Gloria E O; Natarajan, Amarnath (2013. ) The paradox of conformational constraint in the design of Cbl(TKB)-binding peptides.Scientific reports, , 3 ,1639 More Information
Kumar, Eric A; Yuan, Ziyan; Palermo, Nicholas Y; Dong, Lin; Ahmad, Gulzar; Lokesh, G L; Kolar, Carol; Kizhake, Smitha; Borgstahl, Gloria E O; Band, Hamid; Natarajan, Amarnath (2012. ) Peptide truncation leads to a twist and an unusual increase in affinity for casitas B-lineage lymphoma tyrosine kinase binding domain.Journal of medicinal chemistry, , 55 (7 ) ,3583-7 More Information
Rajule, Rajkumar; Bryant, Vashti C; Lopez, Hernando; Luo, Xu; Natarajan, Amarnath (2012. ) Perturbing pro-survival proteins using quinoxaline derivatives: a structure-activity relationship study.Bioorganic & medicinal chemistry, , 20 (7 ) ,2227-34 More Information
Palermo, Nicholas Y; Natarajan, Amarnath (2011. ) Beyond the frog: the evolution of homology models of human IKKβ.Bioorganic & medicinal chemistry letters, , 21 (20 ) ,6081-4 More Information
Yuan, Ziyan; Kumar, Eric A; Campbell, Stephen J; Palermo, Nicholas Y; Kizhake, Smitha; Mark Glover, J N; Natarajan, Amarnath (2011. ) Exploiting the P-1 pocket of BRCT domains toward a structure guided inhibitor design.ACS medicinal chemistry letters, , 2 (10 ) ,764-767 More Information
Yuan, Ziyan; Kumar, Eric A; Kizhake, Smitha; Natarajan, Amarnath (2011. ) Structure-activity relationship studies to probe the phosphoprotein binding site on the carboxy terminal domains of the breast cancer susceptibility gene 1.Journal of medicinal chemistry, , 54 (12 ) ,4264-8 More Information
Kumar, Eric A; Charvet, Casey D; Lokesh, G L; Natarajan, Amarnath (2011. ) High-throughput fluorescence polarization assay to identify inhibitors of Cbl(TKB)-protein tyrosine kinase interactions.Analytical biochemistry, , 411 (2 ) ,254-60 More Information
Chen, Qianyi; Bryant, Vashti C; Lopez, Hernando; Kelly, David L; Luo, Xu; Natarajan, Amarnath (2011. ) 2,3-Substituted quinoxalin-6-amine analogs as antiproliferatives: a structure-activity relationship study.Bioorganic & medicinal chemistry letters, , 21 (7 ) ,1929-32 More Information
Lokesh, G L; Muralidhara, B K; Negi, Surendra S; Natarajan, Amarnath (2007. ) Thermodynamics of phosphopeptide tethering to BRCT: the structural minima for inhibitor design.Journal of the American Chemical Society, , 129 (35 ) ,10658-9 More Information
Presentations
Invited Presentations