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Vaibhav Shinde
Phone. +919673333731
shindev@uni-koeln.de,
vaibhavsshinde@rediffmail.com
Current : 3 9 Robert Koch Street, 50937
, Cologne, Germany
Phone. +49 15217291040
Permanent: 15 VenkateshPlaza,
Pune 411043, India
Summary:
I am professional experimental biologist, whose goal is to harbor highest return of leading scientific
discoveriesintoclinical cures.Inpast 10+ yearsintothe lab,I have contributedindevelopmentof target
specific molecules for cancer, establishment of stem cells and transcriptomics based models for
developmental toxicity. Ihave gainedprofessional level expertise in stem cell biology, cancer biology,
and used it for drug discovery. In addition, I have over 10+ scientific publications.
Education
Dr. rer. med. (Ph.D.);University of Cologne,Germany (2012- 2016)
Supervisor:Prof.Dr.AgapiosSachinidis
Thesis - ‘Establishmentof a stem cell based teratogenicity prediction testsystembased on the
“Dp” and the “Di”
M.V.Sc.:Pharmacology,1999, Mumbai- KKVD(82.50%)
Supervisor:Prof.Dr.Madhu Gatne
Thesis ‘PKstudiesof Chloramphenicolin Buffaloes’
B.V.Sc.& AH, 1997, Mumbai- KKVD(74.60%)
DiplomainBusinessManagement,Chennai-AIIMS(72.00%)
Laboratory Skills
Cell-Culture /MolecularBiology/Biochemistry: Cancercell culture, Stemcell culture & differentiation;
Transfections; Cell growth & cytotoxicity; Cell cycle analysis; Flow cytometry & sorting; Fluorescence
Microscopy, RNA interference & shRNA mediated gene suppression; PCR,
Bioinformatics/Biostatistics: Microarray data analysis, Image analyses.
Instrumentation: Apotome; Spectramax; Affymetrix genearray; BD-FACS; Nanodrop-
Spectrophotometer; Kodak-Image station; ABI-Real-time PCR; HPLC – Merck; LCMS/MS- API3000
In vivo : Xenograft/allograft/metastasismodelswith SCID/Nude/C57BL/swiss mice for efficacy testing
(tumor inhibition or regression/PD). Snap shot PK studies with swiss mice/wistar rats.
Industrial training
Work title Institute details Research details Period
Research
Scientist /
Sr. Research
Scientist
Lupin Limited (Research Park),
Pune 412 115, India Preclinical drug
discovery-
in vitro/ in vivo cancer
models, in vitro/ in
vivo PK studies
Jan. 2007 to
May. 2012
Sphaerapharama Pvt. Ltd.,
Haryana 122051, India
Piramal Life Sciences Ltd.,
Mumbai 400 063, India
Jr. Sci. Asst. /
A.H.T.
Central Drugs Testing Laboratory,
Mumbai 400 008, India
Drugs quality control
in vitro / in vivo testing
Sept. 2000 to
Jan. 2007
Registration
officer
United Phosphorus Ltd. (UPL),
Mumbai 400 052, India
In vivo toxicological
studies evaluation
Dec. 1999 to
Sept. 2000
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Publications
1) Shinde V,HoeltingL,SrinivasanSP, MeisigJ, MeganathanK,JagtapS, GrinbergM, LiebingJ,Bluethgen
N, Rahnenfuhrer J, Rempel E, Stoeber R, Schildknecht S, Forster S, Godoy P, van Thriel C, Gaspar JA,
HeschelerJ,WaldmannT,HengstlerJG,LeistM, Sachinidis A;Definitionoftranscriptome-based indices
for quantitative characterization of chemically disturbed stem cell development: Introduction of the
STOP-Toxukk and STOP-Toxukn tests: Archives of toxicology 2016, doi 10.1007/s00204-016-1741-8
2) Shinde V, Brungs S, Henry M, Wegener L, Nemade H, Rotshteyn T, Acharya A, Baumstark-Khan C,
Hellweg CE, Hescheler J, Hemmersbach R, Sachinidis A;Simulated microgravity modulates
differentiation processes of embryonic stem cells: Cell Physiol Biochem. 2016 Apr 4; 38(4):1483-1499
3) Shinde V,KlimaS, SureshkumarPS,MeganathanK,JagtapS, Rempel E, Rahnenfuhrer J, Hengstler JG,
Waldmann T, Hescheler J, Leist M, Sachinidis A; Human pluripotent stem cell based developmental
toxicityassays for chemical safety screeningandsystems biologydata generation:Journal of visualized
experiments 2015:e52333. doi: 10.3791/52333
4) Shinde V, Brungs S, Hescheler J, Hemmersbach R, Sachinidis A; Pipette-based method to study
embryoid body formation derived from mouse and human pluripotent stem cells partially
recapitulating early embryonic development under simulated microgravity conditions: Microgravity
Science and Technology 2015 doi: 10.1007/s12217-015-9469-2
5) Shinde V, Srinivasan SP, Henry M, Rotshteyn T, Hescheler J, Rahnenfuhrer J, Grinberg M, Meisig J,
Bluethegen N, Leist M, Waldmann T, Hengstler JG, Sachinidis A ; Comparison of teratogenic
transcriptome-based prediction test based on human embryonic versus inducible pluripotent stem
cells : Stem Cell Research & Therapy - manuscript accepted for publication.
6) Rempel E,HoeltingL,Waldmann T, Balmer NV, Schildknecht S, Grinberg M, Das Gaspar JA, Shinde V,
Stober R, Marchan R, van Thriel C, Liebing J, Meisig J, Bluthgen N, Sachinidis A, Rahnenfuhrer J,
Hengstler JG, Leist M; A transcriptome-based classifier to identify developmental toxicants by stem
cell testing: Design, validation and optimization for histone deacetylase inhibitors: Archives of
toxicology 2015;89:1599-1618
7) ChakrabortyJB, Mahato SK,Joshi K, Shinde V,RakshitS,Biswas N, Choudhury Mukherjee I, Mandal L,
Ganguly D, Chowdhury AA, Chaudhuri J, Paul K, Pal BC, Vinayagam J, Pal C, Manna A, Jaisankar P,
Chaudhuri U, Konar A, Roy S, Bandyopadhyay S; Hydroxychavicol, a piper betle leaf component,
induces apoptosis of cml cells through mitochondrial reactive oxygen species-dependent jnk and
endothelial nitric oxide synthase activation and overrides imatinib resistance: Cancer science
2012;103:88-99
8) Wagh V, MishraP, Thakkar A, Shinde V, Sharma S, Padigaru M, Joshi K; Antitumor activity of npb001-
05, an orally active inhibitor of bcr-abl tyrosine kinase: Frontiers in bioscience (Elite edition)
2011;3:1349-1364
9) Shinde V,StoberR,Nemade H,SotiriadouI,HeschelerJ,Hengstler J, Sachinidis A; Transcriptomics of
hepatocytestreated with toxicantsfor investigatingmolecularmechanismsunderlyinghepatotoxicity:
Methods in molecular biology (Clifton, NJ) 2015;1250:225-240
10) Shinde V, Chaudhari U, Sotiriadou I, Hescheler J, Sachinidis A; In vitro methods for cardiotoxicity
testing: In vitro toxicology systems in Bal-Price A, Jennings P (eds)New York, NY, Springer New York,
2014, pp 45-77
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11) Shinde V, Poornima S, Sotiriadou I, Hescheler J, Sachinidis A; Human embryonic and induced
pluripotent stem cell based toxicity testing models : Future applications in new drug discovery: Curr
Med Chem 2016 – doi CMC-EPUB-76855 [pii]
Professional Society
IndianSocietyforVeterinaryPharmacologyandToxicology (ISVPT)
Committee forthe Purpose of Control andSupervisionof Experimental Animals(CPCSEA)
ConsortiumsProjects Worked(Europeancommission/ESA)
ESNATS:Embryonicstemcell basednovel alternative testingstrategies
SysDT: Systemsbiology-basedpredictionof developmental toxicity
ESMESD: Effectof simulatedmicrogravityonembryonicstemcellsdifferentiation
Otherprojectswere relatedtoPI3Kinhibitors,MEKinhibitors,Prodrugs&Nanoparticles.
Managerial experience
In vivo – Significant contribution in laboratory animal house infrastructure construction, CPCSEA
registration, management of laboratory animal house (SCID/Nude/Swiss/C57BL mice, SD rats, NW
rabbits) including equipments purchase, day to day activities, animal import etc.
In vitro – Management of day to day activities involved in mammalian tissue culture lab.
Project funding – The project “ESMESD” conceptualized from own experimental results, wrote the
project, got sanctioned ( 50k euros) and successfully completed under supervision of Professor
Sachinidis.
Summary of research experience/projects
Stem cell research
Establishmentof in vitro assay forteratogenicitytesting(STOP- Toxukk)
Early embryonic development was partially captured by transcriptome profile of hESCs and
hiPSCs after 14 days of differentiation (H9, IMR-90, Foreskin).
To expose cells with teratogenic compounds, the benchmark concentration (BMC) was
determined with resazuin assay on 14 days of H9 differentiation (6 HDACis and mercurials).
The transcriptomicsdataobtainedafter14 daysof drugsexposure atBMC. The novel conceptof
two indices namely “developmental potency” and” developmental index” (Dp & Di) was
established from transcriptomics data to predict teratogenic hazard of compounds.
The transcriptome profile afterValproicacid(VPA) exposure inhESCsandhiPSCs was obtained.
The uniform Di values were obtained across the cell lines indicated its applicability for
determination of the teratogenic hazard.
The VPA deregulated important genes such as FOXC1, VSNL1, ADAMTS9, EBF1, SNAI2 & SULF1
were identified. These genes also similarly deregulated in human patient samples of genetic
disorders(online GEO data sets analysis). These genes are related with the congenital defects
(heart defects -ASD, VSD and neural tube defects) and need to be further studied.
in vitro model for cardiotoxicity testing
The hESCs (H3, H9) and hiPSCs (IMR-90, Foreskin) were differentiated to the cardiomyocytes
(with the sequential exposure to GSK3 inhibitor and Wnt inhibitor).
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The drug VPA/ Thalidomide was exposed during the differentiation. To observed effect on
differentiation, the relative gene expression was determined in pilot study (HAND1, GATA6,
FOXC1, FOXC2, etc.). Further characterization is ongoing.
Effect of simulated microgravity on mESCs differentiation
The pipette basedmethodwasdevelopedforadaptationonthe 2D-clinostatinwhichCGR8cells
were randomly differentiated in pipette.
The transcriptome profile obtained after 3 days exposure revealed microgravity induced
deregulation of genes related to the cytoskeleton and cardiac development.
Cancer research
Established ectopicxenograftmodelswith different cell lines in SCID / Nude mice screening of
new chemical entities (NCEs).
Establishedexperimental metastasismodelswithB16F10, MelJusoandSaos2 LM7 for screening
of anticancer molecules intended for intranasal delivery.
Demonstrated that Paclitaxel resistant cell line (HCT15) is more sensitive to Paclitaxel-
nanoparticles than Taxol in xenograft studies.
Performed in vivo efficacy studies for natural compound NPB001-05 with T315I xenograft and
found more efficacious than Imatinib (NPB001-05 entered in clinical trials).
The cell lines cultured for xenograft - HCT116 (PIK3CA mutant), U87MG (PTEN null), A2780
(PIK3CA mutant, PTEN mutant), H460, HCT15 (paclitaxel resistant cells line- MDR1 over
expressed), Panc 1, PC3 (PTEN null), A549 (activated AKT), etc.
Pharmacokinetic studies (PK) & quality control
Execution of in vitro PK studies like plasma protein binding, microsomal stability, plasma
stability,solubilitytestingwithnephelometeretc.foradvancementof NCEs to in vivo studies in
preclinical drug discovery.
Execution of in vivo PK studies in mice. The PK studies conducted with the pro-drugs
demonstratedspecificpro-drugwithimproved bioavailability and half-life of parent drug. This
helped medicinal chemist to identify pro-drug structure to improve PK properties.
Bio-analytical method development to support PK studies (HPLC and LCMS-MS API-3000).
Execution of various in vitro, in vivo and ex vivo studies as per various pharmacopoeias for
quality control of generic drugs, formulations and cosmetics (Bacterial endotoxin test,
antibacterial assayslike cup-plate/ turbidometric, pyrogen testing in rabbit, abnormal toxicity
testing in mice, skin irritation test, isolated rat uterus for oxytocin assay, etc.).
Research Interests
Cancer research – new drug discovery, translation from bench to bed (in vitro to in vivo clinic)
Understanding fate of epigenetic changes in stem cell differentiation and tumor progression.
Development of stem cell based assays to model disease in petri-plate/ toxicity testing and
advancement of efficacious /safe drugs to clinic.
Directed differentiation of stem cells to the somatic cells.
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References
Prof. AgapiosSachinidis, Universityof Cologne,Instituteof Neurophysiologyand
CenterforMolecularMedicine Cologne (CMMC)
Robert-Koch-Str.369,50931 Cologne,Germany
Email:a.sachinidis@uni-koeln.de
Phone:+49 (0) 221 478 7373
Dr. VilasWagh GeneticsandPhramacogenomics
Merck & Co. 33 Ave.LouisPasteur
BostonMA 02115
Email:vilas.wagh@merck.com
Phone:415.335.8527
Prof. Jan Hengstler IfADo- Ardeystrasse 67- D-44139,
Dortmund44139 - Germany
E-mail:hengstler@ifado.de
Phone.:+49 (0)231 / 1084 348
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December 20, 2016 . Vaibhav Shinde