Welcome to Nanomedicine and Molecular Imaging Laboratory! Let me introduce myself as an interdisciplinary researcher, who aspires to apply her cross-disciplinary skill-sets for developing potential solutions to human health issues. I have just joined the Institute of Health Science as an Assistant Professor. Originally trained as a synthetic organic chemist, I have spent more than a decade in the field of cancer nanomedicine and biomedical imaging. My doctoral and early postdoctoral research at IIT Kharagpur, and NIPER Mohali, primarily focused on the formulation, characterization and in vivo evaluation of a variety of novel drug delivery systems based on biopolymers, lipids, carbon nanotubes and magnetic nanoparticles.In 2013, I joined the Shih Lab at University of North Carolina (UNC), Chapel Hill to gain specialized training in preclinical imaging, which is crucial for new drug development especially for the identification of new druggable targets, evaluation of biodistribution and appropriate dosing strategies, assessment of efficacy and off-target effects, and selection of appropriate patient cohorts for initial testing. In 2014, I received the NIH-sponsored Multimodal Neuroimaging Training Program (MNTP) award by University of Pittsburgh, which allowed me to spend 6 week at CMU and UPMC learning various neuroimaging modalities including fMRI, DTI, MEG, EEG, PET and optical imaging. During this time, I also mastered various pharmacokinetic modeling techniques to interpret clinical PET data from glioma patients. Initially, my research at UNC focused on dissecting the neuronal and glial components of BOLD-fMRI signal using optogenetic and chemogenetic fMRI. Later, I combined chemogenetics with pharmacological fMRI and 18F-FDG PET to decipher the functional projections of genetically distinct subpopulations of central norepinephrine neurons regulating complex behavioral and physiological processes in vivo. I had also integrated my formulation skills with current imaging experience to build a dedicated Contrast agent and Molecular MRI core facility at CAMRI that provided cost-effective solutions and consultancy to preclinical researchers worldwide using nanoparticles for several diagnostic applications including cerebral blood volume (CBV)-fMRI, micro-MR angiography, simultaneous fMRI-fiber photometry, magnetomotive ultrasound imaging and in vitro cell labeling. As the focus of modern medicine is gradually shifting towards a "smart drug" or personalized medicine paradigm, there is an increased demand for amalgamating diagnosis and therapy on the same platform. In such a scientific panorama, I would like to direct my future research toward building a highly translational research program on molecular theranostics, emphasizing on cancer, neurodegenerative disorders, and infectious disease management.
Postdoctoral Research:
- Director of Contrast Agent and Molecular MRI research, Center for Animal MRI (CAMRI), at the University of North Carolina (UNC) Chapel Hill, 2015-2020
- Cross-Disciplinary Fellow (HFSP-CDF) at the Department of Neurology, and Biomedical Research Imaging Center, UNC Chapel Hill, 2013-2018
- Summer Intern, Multimodal Neuroimaging Training Program (MNTP) at University of Pittsburgh Medical Center (UPMC), June-July 2014
- Research Scientist at Center for Pharmaceutical Nanotechnology, NIPER Mohali, 2010-2013
Educational:
- BSc: Chemistry (Hons), Burdwan University, 2003
- MSc: Chemistry, Indian Institute of Technology (IIT) Kharagpur, 2005
- PhD: Indian Institute of Technology (IIT) Kharagpur, 2011 on Design, Synthesis, and Biofunctionalization of Iron Oxide Nanoparticles for Cancer-Specific Targeting, Imaging, and Therapy.
My journey as a researcher
I started my research career as a summer intern in the Bioorganic Chemistry Laboratory at IIT Kharagpur under the able guidance of Prof. Amit Basak. While pursuing my MSc project in his laboratory, I developed a solid foundation in synthetic organic chemistry and associated techniques. I was exposed to a variety of bio-conjugation techniques that are crucial for mild as well as site-specific derivatization of a plethora of bio-molecules including proteins, DNA, RNA, and carbohydrates My Master's dissertation focused on the chemoenzymatic synthesis of intermediates to nucleoside analogues - an important class of antiviral agents that are commonly used in the therapy of human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV), hepatitis C virus (HCV), herplex simplex virus (HSV) and so on. To the beginning of my Ph.D., I started working on a project that aimed to exploit magnetic nanoparticles for hyperthermic activation of ene-diynes in cancer cells. This was the starting point of my interest in drug delivery and theranostics. Subsequently, I started developing a variety of iron-oxide based nanoformulations that were conjugated to multiple bioactive entities such as folic acid (a cancer targeting agent), methotrexate (anticancer drug) and rhodamine isothiocyanate (a fluorophore). These nanoformulations were able to track, target, and kill cancer cells in vitro.
During my PhD, I developed a variety of iron-oxide based nanoformulations for diagnostic and drug delivery purposes; unfortunately, due to infrastructural constraints and lack of appropriate training, I was unable to evaluate their efficacy in vivo. To enhance my in vivo experience, after the submission of my PhD dissertation, I joined the Center for Pharmaceutical Nanotechnology, NIPER Mohali (Feb 2010-June 2013) as a research scientist. At NIPER, I accumulated substantial experience in the development of novel drug delivery systems and therapeutic bioconjugates for targeting cancer, diabetes and fungal infections. During this time, I worked on the synthesis, functionalization and characterization of a wide variety of nanoparticles which included carbon nanotubes, polymeric nanoparticles, solid lipid nanoparticles (SLN), self nano-emulsifying drug delivery systems (SNEDD), liquid crystalline nanoparticles (LCNP), protein-based (albumin) nanoparticles and so on. I also got a chance to test the pharmacokinetics, pharmacodynamics, and toxicity of these nanosystems in chemically induced breast cancer and diabetic rat models. In 2013, to gain further expertise in biomedical imaging, I joined UNC Chapel Hill as a postdoctoral research associate, where I started working with Dr. Yen-Yu Ian Shih, the Director of Center for Animal MRI (CAMRI) and an associate professor in the departments of Neurology, Biomedical Research Imaging Center (BRIC) and Biomedical Engineering.
A major motivation of my postdoctoral training at UNC was to build a unique research track focused on molecular theranostics. My research at UNC encompassed two major directions – 1) Developing multimodal contrast agents/ molecular imaging probes for a range of diagnostic and theranostic applications; 2) Dissecting neuronal circuitry underlying various complex behaviors and neuropsychiatric disorders using chemogenetic fMRI, optogenetic fMRI and PET. In course of pursuing these projects, I gained considerable experience with-
- high field (9.4T) MRI operation
- MRI physics and basic MRI hardwares (e.g. fabrication of MRI brain coil, holder design etc.)
- fluorescence-based microscopic techniques for histological validation of imaging results
- various in vivo techniques on rodents (including different types of survival surgeries)
- MRI data acquisition and optimization of a range of MR imaging protocols including BOLD fMRI, continuous arterial spin labeling (CASL) for simultaneous determination of BOLD and cerebral blood flow, cerebral blood volume fMRI, manganese-enhanced MRI (MEMRI), T1 and T2 mapping/ Relaxometry, DSC and DCE-MRI, high resolution micro-MR angiography, resting-state functional connectivity MRI and Magnetic Resonance Spectroscopy.
To further gain expertise in other imaging modalities, I applied to and was selected for a highly competitive NIH-sponsored Multimodal Neuroimaging Training Program (MNTP), organized by University of Pittsburgh and Carnegie Melon University. At MNTP, we were introduced to the fundamental principles and modus operandi of various neuroimaging modalities such as fMRI, DTI, MEG, EEG, NIRF and optical imaging. Additionally, I spent 5 weeks at UPMC Hospital, where we had intense training on
- fundamental PET physics, basic radiochemistry, PET data acquisition, processing and analysis
- application of positron emission tomography (PET) in neuro-oncology. Specifically, we performed a team project, where we assessed the clinical outcomes of Temozolide therapy in glioma patients with 18F-fluorothymidine (FLT) PET and compared the results with 18F-fluorodeoxyglucose (FDG) PET (abstract and poster enclosed) using tracer kinetic modeling.
To facilitate my research projects at UNC, I also equipped myself with various software-based image analysis skills involving AFNI, FSL, ITK-SNAP, FEAT, ANTS, AMIRA, PMOD and MATLAB. Cumulatively, throughout my stay at UNC, I mastered a wide array of skill-sets that are necessary to become an independent imaging scientist. My research on chemogenetic fMRI and PET brought me the highly prestigious Cross Disciplinary Fellowship (CDF) award from Human Frontier Science Program Organization (HFSPO) and Summa cum Laude Merit Award from International Society of Magnetic Resonance in Medicine (ISMRM) in 2014 and 2017, respectively. I also amalgamated my expertise in nanomaterial synthesis with imaging skills to establish a dedicated Contrast Agent and Molecular MRI core service and research unit at CAMRI from absolute scratch. This facility used to offer - 1) contrast agent support to imaging scientists all over the world and 2) help our fellow researchers to evaluate the efficacy of their newly developed imaging probes through experimental design, consultancy and analysis support. My team at UNC comprising of several undergraduate students and research technicians succeeded to develop various types of cost-effective nanoformulations that showed promise for a range of preclinical applications including high resolution micro magnetic resonance angiography, cerebral blood volume-weighted functional MRI, hyperpolarized gas MRI, cell labeling, liver and lung imaging and contrast-enhanced magnetomotive ultrasound imaging (MMUS). I hope that my expertise in contrast agent development, molecular imaging, and drug delivery will add a new dimension to the ongoing research and teaching program at the Institute of Health Science, and we, together would be capable of building a highly translational, and interdisciplinary research program.
Awards and Honors
- 2019: Invitation to join Consultative Group of Primary Scientific Advisor, Govt. of India. Working on National Science Policy on various socio-economic issues.
- 2017: Summa Cum Laude Merit Award from International Society for Magnetic Resonance in Medicine (ISMRM, the largest meeting in the world dedicated to MRI) for the work, “Chemogenetic fMRI and 18F-FDG PET Reveal Functional Projections of Hoxb1-Derived Noradrenargic Neurons”.
- 2015, 2016, 2017: Educational Stipend Award for 3 consecutive years for significant contribution in the area of chemogenetic fMRI and new MRI contrast agent development.
- 2014-2017: Cross disciplinary fellowship (CDF) grant award (160,000$) from international Human Frontier Science Program Organization (HFSPO) for dissecting the neuronal and astrocytic component of BOLD-fMRI signal using chemogenetic and optogenetic fMRI
- 2014: Training award (2500$ + Travel stipend) for participation in the highly competitive NIH-sponsored Multimodal Neuroimaging Training Program at University of Pittsburgh and Carnegie Melon University
- 2012: International travel grant award, Indian Council of Medical Research (ICMR), Department of Biotechnology (DBT) and Department of Science and Technology (DST), Government of India (GOI)
- 2012: DST Postdoctoral Fellowship in Nanoscience and Nanotechnology, DST, GOI
- 2011: International travel grant award ICMR and Council of Scientific and Industrial Research (CSIR, GOI)
- 2008: Travel stipend for participation in Science Conclave: A congregation of Nobel Laureates, DST-GOI
- 2005: Junior Research Fellowship (JRF) and Senior Research Fellowship in Chemical Science by CSIR, GOI
- 2003: National Scholarship, GOI for securing 1st class in B.Sc. Final Examination
- 2000: Binoy Krishna Modok Trust Fund Scholarship (Mathematics Topper in High School), Hooghly Mohsin College, India
- 1998: National Prize for securing 55th rank in Secondary (school leaving) Examination among 600000 candidates
Research Experience:
1. July 2013- July 2018: Worked as a post-doctoral research associate (Cross-Disciplinary Fellowship awardee, HFSPO) at the Biomedical Research Imaging Center, UNC-Chapel Hill (US). Developed multimodal contrast agents for advanced brain applications and interrogated neuronal circuits underlying various neuropsychiatric disorders and complex behavior using chemogenetic fMRI, optogenetic fMRI, and chemogenetics-assisted metabolic mapping (PET).
2. June 2014- July 2014: Worked as a summer intern (Multimodal Neuroimaging Training Fellow) at the School of Medicine, University of Pittsburgh. Assessed outcomes of Temozolomide therapy in glioma patients using [18F] FLT and [18F] FDG PET
3. February 2010- July 2013: Worked as a research scientist at the Center for Pharmaceutical Nanotechnology, NIPER – Mohali, India. Developed novel drug delivery systems for targeting cancer, diabetes, and fungal infections. Assessed pharmacokinetics, - dynamics, and toxicity of various nanoformulations in preclinical disease models.
Administrative Experience:
While working as a postdoctoral research associate at UNC-Chapel Hill, I established and managed the Contrast Agent and Molecular MRI Core Facility at the Center for Animal MRI (CAMRI). I along with my team of undergraduate students, and research technicians developed various cost-effective nanoformulations for application in magnetic resonance angiography, cerebral blood volume-fMRI, hyperpolarized gas MRI, simultaneous MR and optical imaging, cell labeling, and magnetomotive ultrasound imaging. This core extended contrast agent support and efficacy evaluation service for new probes to research groups within UNC as well as prominent investigators from Stanford University (US), Emory University (US), NIEHS, NIH(US), UT San Antonio (US), Huck Institute Life Sci. (US), McGill University(Canada), University of Antwerp (Belgium), The University of Hong Kong (China), University of Queensland (Australia), China Medical University (Taiwan), CharlesRiver Laboratories (Finland), Istituto Italiano di Tecnologia and CSMCRI Bhavnagar(India).
Teaching Interests:
Principles of Organic Chemistry, Bio-conjugation, Structure and Function of Biomolecules, Medicinal Chemistry, Drug Design and Development, Advanced Biomaterials, Nanomedicine and Drug Delivery, Molecular Imaging and Theranostics.
Teaching Experience:
- Served as a graduate teaching assistant in the Department of Chemistry, IIT Kharagpur. Tutored Organic Chemistry courses (CY14001) for 1st year B. Tech students. Co-instructed two Masters’ level laboratory courses on Principles of Organic Synthesis (CY43015) and Organic Synthesis Laboratory (CY59001).
- Founder of WINGS, an e-learning platform for the promotion of STEM education for high school and college students. This online platform was developed to guide the meritorious yet financially challenged students during the COVID-19 pandemic situation to prepare for medical and engineering entrance as well as university examinations. Please check https://www.manasmitascientisician.com/wings for more details.
Research Skills and Competencies
- Chemistry. Organic synthesis, Bioconjugation techniques, Nanomaterial synthesis and functionalization, Laboratory safety and chemical hazard management.
- Formulation. Novel Drug Delivery Systems (NDDS) based on polymeric and protein nanoparticles, liquid crystalline nanoparticles, solid-lipid nanoparticles, hydroxyapatite nanoparticles, liposomes, functionalized carbon nanotubes; Diagnostic and theranostic probes based on magnetic and gold nanoparticles.
- Physicochemical characterization techniques: UV, FTIR, NMR, XRD (Powder diffraction), TEM, SEM, XPS, EDX, HRMAS-NMR, TGDTA, DLS, NTA, HPLC, GC, and Mass Spectroscopy (ESI-MS, MALDI-TOF MS, ICP-MS).
- Imaging modalities: MRI, PET, CT, Two photon microscopy, Whole body optical imaging, fNIR, EEG and MEG
- Preclinical MRI: Substantial experience with Bruker 9.4T Small Animal MRI system. Extensively trained in acquisition and optimization of various MR imaging protocols including BOLD fMRI, continuous arterial spin labeling (CASL) for simultaneous determination of BOLD and cerebral blood flow, cerebral blood volume fMRI, manganese-enhanced MRI (MEMRI), T1 and T2 mapping/ Relaxometry, DSC and DCE-MRI, high resolution micro-MR angiography, resting-state functional connectivity MRI and Magnetic Resonance Spectroscopy.
- Image Analysis. Has significant experience in fMRI and PET data analysis using custom MATLAB-based GUI as well as advanced image analysis software packages such as FSL, FEAT, AFNI, ANTs, ITK-Snap, AMIRA and PMOD
- In vivo techniques: Hands-on experience in handling and restraining of rodents (including both rats and mice); various injection techniques including intravenous, intraperitoneal, subcutaneous and intravitreal; oral gavage feeding; anesthesia (injectables and inhalation); tail nick bleed and tail clip bleed/genotyping; ear notch and ear tag; CO2 Flow meter w/Phys. Euthanasia; orotracheal intubation; ventilation; arterial/venous cannulation; blood sample collection; aseptic techniques; advanced stereotactic brain surgeries for virus and drug injection, optical fiber and electrode implantation in brain for optogenetic/electrical stimulation; development of tumor models by chemical induction and xenografting; pharmacokinetic, pharmacodynamic and toxicological evaluation of therapeutic drugs and novel drug delivery systems in tumor and diabetic animal models.
- Tissue culture and histology. Hands-on experience in brain histology and confocal microscopy. Knowledgeable in a variety of cancer cell culture and immunohistochemical techniques.
1. Full-ISMRM Member of International Society of Magnetic Resonance in Medicine (2018-2019).
2 Trainee member of the International Society of Magnetic Resonance in Medicine (2015-2017)
3. Member of American Heart Association 2014 (2013-2014)
4 Member of American Chemical Society 2011 (2011-2014)
5 Postdoc Member of American Association of Pharmaceutical Scientists (2011-2016)
6. Member of Controlled Release Society, (2011-2012)
Selected Publications:
1. Oyarzabal, E. A$.; Hsu, L.M$; Das, M$; Chao, H; Zhou, J; Song, S; Zhang, W; Smith, K.G.; Siolino, N.R.; Evsyukova, I.Y.; Yuan, H; Lee, S.H.; Cui, G.; Jensen, P.; Shih, Y.Y.I. Chemogenetic activation of Locus Coeruleus Noradrenergic Neurons Modulates the Default Mode Network Science Advances 2022, 8 (17) $ Authors contributed equally and are co-first authors
2. Das, M.* $; Oyarzabal, E. A$., Chen, L; Lee, S.H.; Shah, N; Gerlach, G; Zhang, W; Chao TH, Van Den Berg, N; Liu, C; Donley, C; Montgomery, S.; Shih, Y.Y*. One-Pot Synthesis of carboxymethyl-dextran coated iron-oxide nanoparticles (CION) for preclinical fMRI and MRA applications Neuroimage, 2021, 238, 118213 $ Authors contributed equally * Co-corresponding authors
3. Singha, H.; Sreedharan, S.; Oyarzabal, E.A.; Mahapatra, T.S.; Green, N; Shih, Y.Y.I.; Das, M*, Thomas, J.A.; * Das, A; *, and Pramanik, S.K. Mitochondriotropic Lanthanide Nanorods: Implications for Multimodal Imaging Chem. Commun., 2020, 56 (57), 7945-7948 *Co- Corresponding authors
4. Chen, Y.W., Das, M, Oyarzabal, E.A, Cheng, Q; Plummer, N.W.; Smith, K.G.; Jones, G.K.; Malawsky, D; Yakel, J.L.; Shih Y.Y.I, Jensen, P et. al. Genetic identification of a population of noradrenergic neurons implicated in stress resilience Molecular Psychiatry (Nature Publishing Group) 2019, 24(5), 710-725
5. Decot, H.K; Namboodiri, V.M.K; Gao, W.; McHenry, J; Jennings, J.; Lee, SH.; Kantak, P.; Kao, Y.C.; Das, M.; Witten, I.; Deisseroth, K.; Shih, Y.Y.I; Stuber, G Coordination of brain-wide activity dynamics by dopaminergic neurons Neuropsychopharmacology 2017, 42 (3), 615-627
6. Das, M#; Jain, R#; Agrawal, A.K. et al. Macromolecular bipill of gemcitabine and methotrexate facilitates tumor-specific dual drug therapy with higher benefit-to-risk ratio Bioconjugate Chem. 2014, 25, 501-9 # Authors contributed equally
7. Hatial I; Jana, S; Bisai S; Das M et al. Trienediynes on a 1, 3, 5-trisubstituted benzene template: A New Approach for Enhancement of Reactivity RSC Advance 2014, 4, 28041-28045
8. Das, M; Singh, R.P; Datir S et al. Intranuclear Drug Delivery and Effective in vivo Cancer Therapy via Estradiol PEG-Appended Multiwalled Carbon Nanotubes. Mol. Pharm. 2013, 10, 3404-3416 (58, 4.939)
9. Das, M; Datir, S; Singh, R.P et al. Augmented Anticancer Activity of a Targeted, Intracellularly Activatable, Theranostic Nanomedicine based on Fluorescent and Radiolabeled, Methotrexate-Folic acid-Multiwalled Carbon Nanotube Conjugate Mol. Pharm. 2013, 10, 2543-2557 (109, 4.939)
10. Das, M.*; Mishra, D.; Dhak, P; et al. Biofunctionalized, phosphonate-grafted, ultrasmall iron oxide nanoparticles for combined targeted cancer therapy and multimodal imaging. Small 2009, 5, 2883-2893 (Co-corresponding author)
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