Assistant Professor of Chemical Engineering
B. Tech. Chemical Technology, Institute of Chemical Technology, India, 2003
Ph.D. Chemistry, University of Cincinnati, 2011
Postdoctoral Fellowship, Brigham and Women’s Hospital, Harvard Medical school, 2015
Instructor in Medicine, Harvard Medical School, 2017
Associate Bioengineer, Brigham and Women’s Hospital, 2017
Dysregulated immune system activation is at the root of several diseases: overactivation can lead to autoimmunity and underactivation can lead to immunodeficiency, compromise resistance to infections and allow for the development of malignancy. Our group works at the interface of engineering and immunobiology to develop innovative technologies for achieving the precise level of immune activation to treat diseases and improve human health. Most of our understanding of immune system interactions in diseases is still limited by the lack of proper tools and techniques. We develop ‘ImmunoEngineering’ platforms to understand and quantitatively study the interactions between different components of the immune system in health and disease. To perturb these interactions at a spatial and temporal scale, and efficiently modulate the immune response, we engineer biologically-inspired ‘ImmunoTherapeutics’ by utilizing high throughput computational platform technology. Real-time monitoring of immunotherapy efficacy is an unmet need in clinics. We are developing ‘ImmunoTheranostic’ (therapeutic + diagnostic) platform technology that can enable spatiotemporal delivery of an immunotherapy drug and drug function-activatable imaging agent. This technology can not only allow direct and real-time visualization of immunotherapy effect thereby studying heterogeneity in immunotherapy response but can also be utilized to probe interesting biological questions by real-time monitoring of cellular level immune responses. By bridging individual strengths of diverse disciplines including nanotechnology, organic synthesis, computational chemistry, molecular imaging, mathematical modeling and immunology, we are developing tools and platform technologies to address fundamental and translational questions in human diseases, with a goal of developing paradigm shifting immunotherapy strategies.
1. Pandya H. J., Dhingra K., Prabhakar D.#, Chandrasekar V.#, Natarajan S. K.#, Vasan A. S., Kulkarni A. A.*, Shafiee H.*, “A microfluidic platform for drug screening in a 3D cancer microenvironment.” Biosensors and Bioelectronics, 2017; 94: 632-42.
2. Kulkarni A. A.*, Rao P., Natarajan S., Goldman A., Sabbisetti V., Khater Y., Korimerla N., Chandrasekar V., Mashelkar R.*, Sengupta S.*, “Reporter nanoparticle that monitors its anticancer efficacy in real time.”, Proc Natl Acad Sci U S A, 2016; 1(15): E2104-13. (Highlighted in over 140 news outlets including The Scientist, NanoWerk, Science News, Daily Mail, Yahoo News, The Telegraph and The Herald Sun.)
3. Kulkarni A. A., Natarajan S. K., Chandrasekar V., Pandey P, Sengupta S., “Combining immune checkpoint inhibitors and kinase-inhibiting supramolecular therapeutics for enhanced anti-cancer efficacy”, ACS Nano, 2016; 10(10): 9227-42. (Highlighted in 5 news outlets including Science Daily, Eureka Alert, Nanotechnology Now, Health Medicine Newtork, Phys.org and MedIndia.)
4. Kulkarni A. A., Pandey P, Rao P. S., Mahmoud A., Goldman A., Sabbisetti V., Parcha S., Natarajan S. K., Chandrasekar V., Dinulescu D., Roy S., Sengupta S., “Algorithm for designing nanoscale supramolecular therapeutics with increased anticancer efficacy”, ACS Nano, 2016; 10(9): 8154-68. (Highlighted in ACS Nano as a perspective and over 6 news outlets including Eureka Alert, NanoWerk, Health Medicine Newtork, Phys.org and MedIndia.)
5. Kulkarni A. A. #, Goldman A. #, Kohandel M., Pandey PR., Natarajan S., Ravi S., Sabbisetti S., Sengupta S, “Rationally designed 2-in-1 nanoparticles can overcome adaptive resistance in cancer”, ACS Nano, 2016; 10(6): 5823-5824. (Highlighted in over 20 news outlets including NanoWerk, Science Daily, Health Medicine Newtork, News Medical, eCancer and Bioscience Technology.)
6. Kulkarni A. A.*, Vijaykumar V. E., Natarajan S. K., Sengupta S., Sabbisetti V. S.*, “Sustained inhibition of cMET-VEGFR2 signaling using liposome-mediated delivery increases efficacy and reduces toxicity in kidney cancer”, Nanomedicine: Nanotechnology, Biology and Medicine, 2016; 12(7): 1853-1861.
7. Connor Y., Tekleab S., Husain A., Walls C.,.. Kulkarni A. A., Zetter B., Dvorak H., Sengupta S., “Physical nanoscale conduits-mediated communication between tumor cells and endothelium modulates endothelial phenotype”, Nature Communications, 2015; 16(6): 8671. (Highlighted in over 20 news outlets including The Scientist, MIT News, Harvard News, NanoWerk, Health Medicinet, eCancer, The Telegraph and The Tech Times.)
8. Gaharwar A.K. , Mihaila S. M., Kulkarni A. A., Patel A., Di Luca A., Reis R. L., Gomes M. E., van Blitterswijk C., Moroni L., Khademhosseini A., “Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds”, J Control Release, 2014; 187: 66-73.
9. Kulkarni A. A.*, Roy B., Rao P. S., Wyant G. A., Mahmoud A., Sengupta S.*, “Supramolecular nanoparticles that target phosphoinositide-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy” Cancer Research, 2013; 73(23): 6987-97.
10. Pandey A., Kulkarni A. A., Roy B., Goldman A. J., Sarangi S., Sengupta P., Sengupta S., “Sequential application of a cytotoxic nanoparticle and a PI3K inhibitor enhances antitumor efficacy” Cancer Research, 2014; 74(3): 675-85.
11. Sengupta P., Basu S., Soni S., Pandey A.,.. Kulkarni A. A. et.al. “A cholesterol-tethered platinum II-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity.” Proc Natl Acad Sci U S A, 2012; 109(28): 11294-11299.
12. Sengupta S., Kulkarni A. A., “Design principles for clinical efficacy of cancer nanomedicine: a look into the basics.” ACS Nano, 2013; 7(4): 2878-82.
13. Kulkarni A. A., Fuller C., Korman H., Weiss A. A., Iyer S. S., “Glycan encapsulated gold nanoparticles selectively inhibit Shiga toxins 1 and 2.” Bioconjugate Chemistry, 2010; 21(8): 1486-1493.
14. Kulkarni A. A., Weiss A. A., Iyer S. S., “Detection of carbohydrate binding proteins using magnetic relaxation switches.” Analytical Chemistry, 2010; 82 (17): 7430-7435.
15. Guo X., Kulkarni A. A., Doepke A. Halsall H. B., Iyer S. S., Heineman W. R., “Carbohydrate-based label-free detection of Escherichia coli ORN 178 using electrochemical impedance spectroscopy.” Analytical Chemistry, 2012; 84 (1): 241-246.
16. Flagler M. J., Mahajan S. S., Kulkarni A. A., Weiss A. A., Iyer S. S., “Comparison of binding platform yields insights into receptor binding differences between Shiga toxins 1 and 2.” Biochemistry, 2010; 49(8): 1649-1657.
17. Kulkarni A. A., Weiss A. A., Iyer S. S., “Glycan based high affinity ligands for toxins and pathogen receptors.” Medicinal Research Reviews, 2010; 30(2): 327-393.
Kulkarni A. A.*, Rao P. S., Synthesis of polymeric nanomaterials for biomedical applications. In: Gaharwar A. K., Sant S., Hancock M., Hacking A., editors. Nanomaterials in tissue engineering: characterization, fabrication and applications. Elsevier Publishers (UK); 2013. p. 27-56.