Subrahmanyam Vangala
Advinus TherapeuticsUSA links
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- Drug Metabolism, Pharmacokinetics, Clinical Pharmacology & Investigative ToxicologyBengaluru, India
Dr. Subrahmanyam received his PhD (1987) in Molecular Toxicology from Department of Biochemistry at Memorial University, Canada. Following PhD, he completed 2 year postdoctoral training in the Department of Molecular Toxicology at University of Colorado and heldResearch Assistant Professor Position in the School of Public Health at University of California, Berkeley for 3 years, before joining the industry. He chaired the inaugural Land-O’-Lakes Drug Metabolism and Applied Pharmacokinetics Conference(1998) and 1st and 2nd Idiosyncratic Drug toxicity conferences (1998 and 2000). He gave guest lecturers as invited speaker at several international conferences related to ADME/Predictive toxicology. In 2005 he received Excellence in Science Award from JNJ. Since 2010 serving as editor of the STM Journal of Toxicology: Research and Reviews.Served on international advisory board for journal Current Pharmacogenomics and Personalized Medicine (CPPM-2012 & 2013). He published ~40 research articles and reviews including several invited book chapters.
Research Interest
Drug discovery & development relating to DMPK; Clinical pharmacology; Investigative toxicology; Biomarkers and molecular diagnostics.
Research Experience
Summary
Experienced
professional who excels in both scientific and regulatory expertise for
drug discovery and development success. Strong track record of
accomplishment in building infra-structures and integrating departments
into effective, value-added support for R&D organizational success..
Primary areas of expertise include Toxicology, Pharmacology, DMPK, Bioanalytical, Clinical Pharmacology and Investigative/Mechanistic Toxicology. Experienced in both small molecule and biotechnology-based drug platforms. Some experience with large molecule drug development. Therapeutic areas of expertise include CNS, Neuro-degenerative diseases, Metabolic disorders, Inflammation, Oncology, Anti-infectives and Women's Health (eg, SERMs).
Primary areas of expertise include Toxicology, Pharmacology, DMPK, Bioanalytical, Clinical Pharmacology and Investigative/Mechanistic Toxicology. Experienced in both small molecule and biotechnology-based drug platforms. Some experience with large molecule drug development. Therapeutic areas of expertise include CNS, Neuro-degenerative diseases, Metabolic disorders, Inflammation, Oncology, Anti-infectives and Women's Health (eg, SERMs).
Experience
Vice President, DMPK, Clinical Pharmacology & Investigative Toxicology
Advinus Therapeutics- A TATA Enterprise
Vice President, Pharmacology & Toxicology
Sai Advantium Pharma Ltd, Pune India
In
the last 4 years of my tenure at SAI, I established the infra structure
for drug discovery support services relating to Pharmacology, ADME and
Toxicology screening. Designed the laboratories that included 20,000 SF,
hired about 40 plus scientists (including 5 Associate Directors as
group managers), and established validated protocols for ADMET services,
Supported ADMET services for several biotech companies in US and Europe.
The animal facilities are accredited by Indian CPCSEA and American AAALAC authorities. Selected areas of in vitro and in vivo laboratories are also approved for conducting radiolabel studies. ADME services include in vivo PK in rodents, mass balance, tissue distribution, protein binding, caco-2/mdck permeability, CYP profiling (competitive inhibition,time-based inhibition, phenotyping), metabolic stability, profiling & metabolite ID, GSH-trapping of reactive intermediates, physico-chemical properties (solubility, stability, pka, logP, logD).
Toxicology services include: acute, DRF, pivotal one month tox, (includes: clinical observations, clinical pathology, hematology, histopathology, toxicokinetics), genetic toxicology (AMES, micronucleus tests).
Pharmacology services include radioligand binding assays, cell based assays, in vivo models of pharmacology (pain, neurodegenerative diseases and inflammation)
For a smooth operational excellence, appropriate processes are put in place to avoid delays and ensure high quality and timely delivery of results and reports to the clients.
Communication excellence of all employees is considered number one piority and appropriate training is provided for all departmental personnel.
Safe laboratory practices has been made mandatory with appropriate training recommendations are made for employees by "Health & Safety Environment" department.
Budget projections based on business needs and for strategic growth are provided to senior executives with rational justifications.
Supported ADMET services for several biotech companies in US and Europe.
The animal facilities are accredited by Indian CPCSEA and American AAALAC authorities. Selected areas of in vitro and in vivo laboratories are also approved for conducting radiolabel studies. ADME services include in vivo PK in rodents, mass balance, tissue distribution, protein binding, caco-2/mdck permeability, CYP profiling (competitive inhibition,time-based inhibition, phenotyping), metabolic stability, profiling & metabolite ID, GSH-trapping of reactive intermediates, physico-chemical properties (solubility, stability, pka, logP, logD).
Toxicology services include: acute, DRF, pivotal one month tox, (includes: clinical observations, clinical pathology, hematology, histopathology, toxicokinetics), genetic toxicology (AMES, micronucleus tests).
Pharmacology services include radioligand binding assays, cell based assays, in vivo models of pharmacology (pain, neurodegenerative diseases and inflammation)
For a smooth operational excellence, appropriate processes are put in place to avoid delays and ensure high quality and timely delivery of results and reports to the clients.
Communication excellence of all employees is considered number one piority and appropriate training is provided for all departmental personnel.
Safe laboratory practices has been made mandatory with appropriate training recommendations are made for employees by "Health & Safety Environment" department.
Budget projections based on business needs and for strategic growth are provided to senior executives with rational justifications.
Director, Toxicology and Pharmacology
Shire HGT
Provided
PK and Toxicology support for "Enzyme Replacement Therapy" programs.
Managed outsourcing of all PK and Toxicology studies. Designed and
reviewed protocols, analyzed PK and Toxicology data, reviewed reports,
presented at Senior management meetings. Projected quarterly budgets and
provided appropriate justifications. During this job, I had an
opportunity to learn drug discovery/development processes and associated
regulatory challenges for large molecule biologics.
Site Director/Research Fellow, Drug Metabolism and Pharmacokinetics
Johnson & Johnson
•Built a strong DMPK department from a size of 4 to 28 scientists (Total of 7 PhD: 4 direct reports (2 GL, 1 RS and 1 PS).
•Included experts in compartmental & non-compartmental methods of PK/TK (GLP), allometric scaling, IV/IVC of ADME, metabolite ID (LC/MS), in vitro DDI, absorption, transporter, biliary excretion studies. Evaluation of novel technologies (metabonomics, reactive metabolites, RED for protein binding).
•Established a competitive DMPK Dept, attracting the best talent from major Pharma including Merck, Aventis, Pfizer, Schering, Roche.
•Participated in project teams for preclinical development. Provided preclinical strategies, proposals, and timelines. Provided critical, expert input in go/no go decisions.
•Managed annual DMPK budget of up to 8 MM (USD). Prepared budgets, short/long-term strategies, requested appropriate human and capital resources for dept growth. Balanced in-house and out-sourced activities, with >90% in-house capacity by 2006 compared to <10% in 2001. Justified the purchase of LTQ-Orbitrap to Senior management and finance department and established the state-of-the-art technology for DM studies.
• Active and lead role in the global harmonization of CYP-DDI assays. Identified similarities and differences in processes, assay methods for DDI studies at other JNJ companies. Where needed, harmonized assay protocols in consensus with other DMPK leaders at JNJ.
•Collaborated with Mechanistic Toxicology group to provide DMPK support to address specific project related safety issues. Key management representative for “Hepatotoxicity Expert Group” for evaluation of hepatotoxicity mechanisms.
•Delegated resources to collaborate with CATD (Computer Aided Trial Design) group for PK-PD model development using preclinical data.
•Participated in due-diligence teams for in-licensing candidates by reviewing the Preclinical data packages.
•Successfully completed year long “Management Fundamentals” training course at JNJ.
•Included experts in compartmental & non-compartmental methods of PK/TK (GLP), allometric scaling, IV/IVC of ADME, metabolite ID (LC/MS), in vitro DDI, absorption, transporter, biliary excretion studies. Evaluation of novel technologies (metabonomics, reactive metabolites, RED for protein binding).
•Established a competitive DMPK Dept, attracting the best talent from major Pharma including Merck, Aventis, Pfizer, Schering, Roche.
•Participated in project teams for preclinical development. Provided preclinical strategies, proposals, and timelines. Provided critical, expert input in go/no go decisions.
•Managed annual DMPK budget of up to 8 MM (USD). Prepared budgets, short/long-term strategies, requested appropriate human and capital resources for dept growth. Balanced in-house and out-sourced activities, with >90% in-house capacity by 2006 compared to <10% in 2001. Justified the purchase of LTQ-Orbitrap to Senior management and finance department and established the state-of-the-art technology for DM studies.
• Active and lead role in the global harmonization of CYP-DDI assays. Identified similarities and differences in processes, assay methods for DDI studies at other JNJ companies. Where needed, harmonized assay protocols in consensus with other DMPK leaders at JNJ.
•Collaborated with Mechanistic Toxicology group to provide DMPK support to address specific project related safety issues. Key management representative for “Hepatotoxicity Expert Group” for evaluation of hepatotoxicity mechanisms.
•Delegated resources to collaborate with CATD (Computer Aided Trial Design) group for PK-PD model development using preclinical data.
•Participated in due-diligence teams for in-licensing candidates by reviewing the Preclinical data packages.
•Successfully completed year long “Management Fundamentals” training course at JNJ.
Section Head/Group Leader, Drug Metabolism and Pharmacokinetics
Purdue Pharma
•Managed
8–10 scientists including 4 PhD’s. Established drug metabolism
laboratory that was non-existent at Purdue. Managed the PKDM group,
supported discovery and development projects- including in vitro/in vivo
DM, in vitro DDI, writing preclinical sections for NDA/IND.
•Represented the project teams and sub-teams for DMPK, toxicology, bioanalytical, activities.
•Established hepatocyte cell culture methods, developed cryopreserved hepatocytes banks and validated their use for drug metabolism and CYP induction studies.
•Established HPLC/MS coupled to radiometric detection for metabolite separation and identification to support preclinical and clinical programs.
•Established high throughput screening methods for discovery support - Fluorescence cytotoxicity assays using hepatocytes, bDNA assay for cytochrome P450 induction in hepatocytes.
•Established CYP enzyme ID methods using - correlation analysis, recombinant enzymes and specific inhibitor assays. Developed and validated the use of characterized bank (16 subjects) of human liver microsomes for CYP ID studies.
•Established drug interaction studies using microsomes, recombinant enzymes and hepatocytes. Made recommendations for clinical drug interaction program. Established high-throughput fluorescence P450 inhibition screens for discovery support, Coordinated mass-spec activities for metabolite identification.
•Played key role in help building a Discovery Support program that was non-existent at Purdue. Provided strategies on how a discovery support group could help in lead selection and optimization. Identified industry experts in heading this group.
•Coordinated contract laboratory activities for drug metabolism studies in hepatocytes/microsomes, CYP enzyme ID, induction, inhibition, genotyping and Caco-2 permeability studies.
•Established collaborative efforts with academia for assessing mechanisms of drug toxicity using cellular models and selecting lead candidates from backups.
•Represented the project teams and sub-teams for DMPK, toxicology, bioanalytical, activities.
•Established hepatocyte cell culture methods, developed cryopreserved hepatocytes banks and validated their use for drug metabolism and CYP induction studies.
•Established HPLC/MS coupled to radiometric detection for metabolite separation and identification to support preclinical and clinical programs.
•Established high throughput screening methods for discovery support - Fluorescence cytotoxicity assays using hepatocytes, bDNA assay for cytochrome P450 induction in hepatocytes.
•Established CYP enzyme ID methods using - correlation analysis, recombinant enzymes and specific inhibitor assays. Developed and validated the use of characterized bank (16 subjects) of human liver microsomes for CYP ID studies.
•Established drug interaction studies using microsomes, recombinant enzymes and hepatocytes. Made recommendations for clinical drug interaction program. Established high-throughput fluorescence P450 inhibition screens for discovery support, Coordinated mass-spec activities for metabolite identification.
•Played key role in help building a Discovery Support program that was non-existent at Purdue. Provided strategies on how a discovery support group could help in lead selection and optimization. Identified industry experts in heading this group.
•Coordinated contract laboratory activities for drug metabolism studies in hepatocytes/microsomes, CYP enzyme ID, induction, inhibition, genotyping and Caco-2 permeability studies.
•Established collaborative efforts with academia for assessing mechanisms of drug toxicity using cellular models and selecting lead candidates from backups.
Senior Scientist 1 & 2
American Cyanamid/Wyeth
•As
a principal investigator, conducted extensive hands-on toxicokinetics
analysis in accordance with GLP. Supported all non-GLP and GLP
toxicology including acute, sub-chronic and chronic studies.
•As a study director and principal investigator designed and conducted PK (Bioavailability), mass-balance, protein binding, in vivo/in vitro DM, (CYP isozyme ID, CYP-DDI) studies.
-Conducted hands-on investigative studies to elucidate the mechanisms underlying long plasma 14C-half life (>22 days) of a drug candidate. Collaborated with Analytical Development group to conduct amino acid analysis of plasma proteins and with academia to urinalysis of endogenous metabolic products. The investigations revealed a novel mechanism of one-carbon recycling of carbon released from the drug and incorporation into amino acids, proteins and nucleic acids.
-Conducted hands-on studies and evaluated non-CYP mediated phase-1 and phase 2 DM for selected preclinical drug candidates based on strucutre-activity relations. These enzymes include molybdenum hydroxylases (aldehyde and xanthine oxidses), monoamine oxidases, carboxylesterases, amidases and UDP-glucuronosyl trnsferases.
-Established recombinant human (rh) CYP-isozyme banks (from cDNA expressed E.coli cells) for routine drug metabolism studies. Validated the rhCYP isoforms using standard probe substrates and HPLC analysis.
-Participated in LC-NMR evaluation in collaboration with Bruker for drug metabolism and metabolite-ID studies.
-Supervised two technical assistants. Prepared reports and DM sections of IND/NDA sections for regulatory submissions.
•As a study director and principal investigator designed and conducted PK (Bioavailability), mass-balance, protein binding, in vivo/in vitro DM, (CYP isozyme ID, CYP-DDI) studies.
-Conducted hands-on investigative studies to elucidate the mechanisms underlying long plasma 14C-half life (>22 days) of a drug candidate. Collaborated with Analytical Development group to conduct amino acid analysis of plasma proteins and with academia to urinalysis of endogenous metabolic products. The investigations revealed a novel mechanism of one-carbon recycling of carbon released from the drug and incorporation into amino acids, proteins and nucleic acids.
-Conducted hands-on studies and evaluated non-CYP mediated phase-1 and phase 2 DM for selected preclinical drug candidates based on strucutre-activity relations. These enzymes include molybdenum hydroxylases (aldehyde and xanthine oxidses), monoamine oxidases, carboxylesterases, amidases and UDP-glucuronosyl trnsferases.
-Established recombinant human (rh) CYP-isozyme banks (from cDNA expressed E.coli cells) for routine drug metabolism studies. Validated the rhCYP isoforms using standard probe substrates and HPLC analysis.
-Participated in LC-NMR evaluation in collaboration with Bruker for drug metabolism and metabolite-ID studies.
-Supervised two technical assistants. Prepared reports and DM sections of IND/NDA sections for regulatory submissions.
Research Assistant Professor
UC Berkeley
-Supervised a group of four scientists (1 PhD and 3 graduate students).
-Designed in vitro and in vivo metabolism and molecular toxicology studies using isolated enzyme systems (microsomes, recombinant CYP enzymes, prostaglandin H synthase, myeloperoxidase etc), cell cultures (HL-60 cells, human lymphocytes) and in vivo mouse models.
-Established measurement of oxidative DNA damage techniques for assessing non-genotoxic events in chemical carcinogenesis using HL-60 cells and mouse models (Collaborated with Dr. Bruce Ames laboratory at Department of Biochemistry for measurement of oxidative DNA damage by HPLC-Electrochemical detection methods).
-Conducted mechanistic drug metabolism studies using hemeprotein peroxidases. Investigated novel cooperative interactions of heme and apoprotein in catalyzing drug metabolism.
-Lectured “Chemical Carcinogenesis” course to graduate students.
-Designed in vitro and in vivo metabolism and molecular toxicology studies using isolated enzyme systems (microsomes, recombinant CYP enzymes, prostaglandin H synthase, myeloperoxidase etc), cell cultures (HL-60 cells, human lymphocytes) and in vivo mouse models.
-Established measurement of oxidative DNA damage techniques for assessing non-genotoxic events in chemical carcinogenesis using HL-60 cells and mouse models (Collaborated with Dr. Bruce Ames laboratory at Department of Biochemistry for measurement of oxidative DNA damage by HPLC-Electrochemical detection methods).
-Conducted mechanistic drug metabolism studies using hemeprotein peroxidases. Investigated novel cooperative interactions of heme and apoprotein in catalyzing drug metabolism.
-Lectured “Chemical Carcinogenesis” course to graduate students.
Postdoctoral Research Associate, Envoronmental and Molecular Toxicology, School of Pharmacy
University of Colorado at Boulder
Conducted
hands-on in vitro drug metabolism and molecular toxicology experiments
utilizing hepatocytes. Mastered in-situ liver perfusion techniques for
isolating hepatocytes from rats. Developed techniques for measuring
various biochemical and molecular end- points of cell death (GSH
depletion, ATP depletion, inhibition of protein and RNA synthesis,
covalent binding to proteins and DNA etc.).
Conducted Drug Metabolism and toxicity studies in bone marrow homogenates and bone marrow stromal cells. Evaluated role of cytokines and other growth factors in bone marrow toxicity
Supervised one technician and one graduate student.
Conducted Drug Metabolism and toxicity studies in bone marrow homogenates and bone marrow stromal cells. Evaluated role of cytokines and other growth factors in bone marrow toxicity
Supervised one technician and one graduate student.
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