Gregory T. (Greg) Knipp

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Associate Professor of Industrial and Physical Pharmacy
Associate Director, Dane O. Kildsig Center for Pharmaceutical Processing Research
Phone:
765-494-3765
Fax:
765-494-6545
Specialization: Preclinical drug discovery support, ADMET, Blood-Brain Barrier, and PK/PD

Education

BS Biochemistry, 1988, Cook College, Rutgers, The State University of New Jersey.
MS Pharmaceutical Chemistry, 1995, The University of Kansas
PhD, Pharmaceutical Chemistry, 1997, The University of Kansas
Post-Doctoral Fellow, Department of Integrative and Molecular Physiology, The University of Kansas - Medical Center 1997-1999

Research

Dr. Knipp's laboratory is dedicated to the utilization of new and improved models for assessing pharmaceutical performance.  The laboratory's research interests include  preclinical in vitro and in vivo ADMET screening, physicochemical characterization, early formulation development, and performing pharmacokinetic studies of new cand traditional chemical entities.  

His laboratory has been recently focused on the development of a novel, direct contact human blood brain barrier triculture model for screening permeability-linked neuroactivity. Cultured in the presence of neurons, this flexible platform in vitro model has been applied to assess neurotoxicity and screening compounds with an observed neurotherapeutic/neurotoxic effect. This project is currently funded by the EPA. 

His laboratory has also been collaborating on two significant NIH funded projects: 1) an R01 on the development of novel antiviral compounds with the potential to treat Ebolavirus; and 2) a larger, multi-institutional U54 grant aimed at developing agents that may provide rapid rescue from cyanide exposure. 

Dr. Knipp also  currently serves as the faculty director of the Purdue Translational Pharmacology (PTP) CTSI Core Facility, where he  maintains a strong interest in the utilizing rodent and juvenile and adult porcine models for testing the pharmacokinetics formulations under stress free conditions. 

Lab Members

Matthew Behymer (Graduate Student with Dr. Gregory Knipp)
Charlie C. Zhang (Research Technician)

Service and Engagement

Faculty Director of the Purdue Translational Pharmacology (PTP) CTSI Core Facility

Teaching

IPPH 45100 Industrial Practical Training

IPPH 58300  Advanced Biopharmaceutics

PHRM 828 Dosage Forms I

PHRM 866 Biotech/Advanced Parenteral Dosage Forms

Grants

RESEARCH AND TEACHING GRANTS:

Active 

Aug. 2020-July 2022 - Environmental Protection Agency, (PI) $790,441, OSAPE Star Grant, “Integrated Blood Brain Barrier-Computational Model Development to Predict Doses of Concern for Compound Linked Neurotoxicity.”

Aug. 2019-Aug. 2023 - National Institute of Allergy and Infectious Diseases (R01 AI128364-01A1), (Co-PI; Davisson PI), “Antiviral Lead Identification to Treat Filovirus Infections.” 

July 2019 - June 2024 - National Institute of Neurological Disorders and Stroke-CounterACT Centers of Excellence (U54 NS079201-06A1), (Purdue Co-I; Davisson PI), “Discovery and Development of Novel Classes of Cyanide Countermeasure.”

November 2018-October 2020 - Purdue University, the Institute for Drug Discovery (PIDD), Programmatic Area Grant, (Co-I), “The Development of Novel FLT3 Inhibitors for the Treatment of Acute Myeloid Leukemia.” 

November 2018-October 2020 - Purdue University, the Institute for Drug Discovery (PIDD), Programmatic Area Grant, (Co-PI), “Development of a Novel BBB-on-a-chip Model to Improve Selection of Therapeutics.” 

Sept. 2010-Present - The Indiana Clinical Translational Sciences Institute, Faculty Director (Co-PI), “Establishment of the Purdue Porcine Translational Pharmacology Core.”

Presentations

SELECTED PRESENTATIONS:

“In Vitro Neurovascular Unit Model: Assessing Permeability-Linked Neuroactivity” Hosted by Dr. Aaron Bowman, 2019 Parkinson Interest Group Meeting, West Lafayette, IN, October 2019.

“Establishing a Physiologically Relevant In Vitro BBB Permeability and Neuroactivity Screening Model” Hosted by BioCrossroads, 2019 Life Sciences Summit, Indianapolis, IN, September 2019.

K. Lubin, M. Behymer, G.T. Knipp. “Design of Experiments Approach for the Optimization of a Physiologically Relevant In Vitro Blood Brain Barrier Model.” 22nd International Symposium on Signal Transduction at the Blood-Brain Barriers. Organized by Fraunhofer Inc., Wurzburg, Germany, September (2019).

 “Mini-tablet Formulations and Pharmacokinetics in the Porcine Model: Expediting Pediatric Drug Development.” Hosted by Dr. Scott Hostetler, Elanco, Greenfield, IN, July 5, 2018.

K. Lubin, C.D. Kulczar, A. Ngendahimana, G.T. Knipp. Development and Optimization of a Direct Contact Blood Brain Barrier Model for In Vitro Permeability Screening. 2018 Globalization of Pharmacy Education Network (GPEN) Meeting. Organized by The National University of Singapore, Singapore, October (2018).

K. Lubin, G.T. Knipp. Development and Optimization of a Direct Layered Contact Blood Brain Barrier Model for In Vitro Permeability Screening. World Preclinical Congress: Blood Brain Barrier, Boston, MA (2018).

C. Popescu, R.P. Gala, G.T. Knipp, R.R. McCain, and M.J. D’Souza. ODF (Oral Disintegrating Film) as a Pediatric Centric Delivery System. 9th European Paediatric Formulation Initiative Conference, Warsaw, Poland, September 19-21 (2017)

R.P. Gala, C. Popescu, G.T. Knipp, R.R. McCain, R.V. Ubale, R. Addo, T. Bhowmik, and M.J. D’Souza. Next Generation of Immunization: Oral Disintegrating Films Loaded with Nanoparticulate Measles Vaccine for Buccal Delivery. 10th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Glasgow, U.K. (2016).

“Inert or Functional Pharmaceutical Excipients: Reviewing the Fundamental Basis for Risk in Pediatric and Adult Formulations” Hosted by Dr. Sophie-Dorothee Clas, 2016 M3 Conference: Molecules, Materials, Medicines, Solomons Island, MD. May 2016.

“Elucidating Peptide Permeation Pathways Across In Vitro Models of the Gastrointestinal Epithelial and Blood-Brain Barriers.” A Tribute to Ronald T. Borchardt, The University of Kansas, Lawrence, KS, October 2015

Universidad Autónoma del Estado de Morelos, in Cuernavaca, Morelos, México. Hosted by the AAPS Student Chapter and the Facultad de Farmacia. Presented a short course entitled “Current Trends, Risks, and Opportunities in the Preclinical Translation of Novel Therapeutic Agents.” September 2015.

Mexican National Association of Farmacia, Hosted by Dr. Dea Herrera-Ruiz, "Treating Therapeutic Orphans: Preclinical Challenges to Pediatric Drug Development." 2015 Mexican National and International Congress of Pharmaceutical Sciences, Cancun, Quintana Roo, Mexico, September, 2015.

Eli Lilly Co., Indianapolis, IN. Hosted by Kaoutar Abbou Oucherif. “Risks and Challenges Associated with Pediatric Drug Development: What Role Should/Could Academia Play?” April 22, 2015.

R.P. Gala, C. Popescu, G.T. Knipp, R.R. McCain, R.V. Ubale, R. Addo, T. Bhowmik, and M.J. D’Souza. Needle less Measles Vaccine Delivery: Preclinical Evaluation of Oral Disintegrating Films in a Juvenile Pig Model. 2015 American Association of Pharmaceutical Scientists Annual Meeting, Orlando, FL. (2015).

“Evaluation of the Porcine Model for the Determination of Human Pharmacokinetics”, Invited by Dr. Tonglei Li, Presented at Purdue’s 2015 Symposium on Digital Human for Drug Development (DHD2), West Lafayette, IN, February 25, 2015.

“Pediatric Formulation and Regulatory Challenges: An Academic Perspective.” Presented at The Industry¹s Technical and Regulatory Path Forward for Pediatric Formulations Short Course, ExL Pharma’s 4th Drug Formulation & Bioavailability: Breakthrough Techniques in Optimizing the Screening, Delivery, Solubility, and Stability of Drugs and Biologics to Enhance Product Life Cycles, Boston, MA, January 26, 2015.

“Solubility Enhancing Excipients Functional Effects on Drug Transporters and Metabolizing Enzymes: In Vitro Folklore or In Vivo Reality?” Presented in the AAPS Sunrise Session entitled: “The Excipient Paradox—Interaction of Solubilizing Excipients with Metabolizing Enzymes and Transporters.” 2014 American Association of Pharmaceutical Scientists Annual Meeting, San Diego, CA, November 5, 2014.

Development of Pediatric Formulations: Challenges and Opportunities. “Pediatric Clinical Pharmacology and Development: Assessing the Juvenile Swine as a Preclinical Animal PK Model.” 49th AAPS Arden Conference, Rockville, MD. February 24-26, 2014.

Representative Publications

http://www.ncbi.nlm.nih.gov/pubmed/?term=knipp+gt

Purdue PTP webpage:                                                                                                                                           https://www.indianactsi.org/news/purduetranspharm

M Lavan, SR Byrn, GT Knipp. Pediatric Formulations: Knowledge Gaps Limiting the Expedited Preclinical to Clinical Translation in Children. AAPS PharmSciTech 20(2):73, 2019.

J Morningstar, J Lee, T Hendry-Hofer, A Witeof, LT Lyle, G Knipp, et al. Intramuscular Administration of Hexachloroplatinate Reverses Cyanide-Induced Metabolic Derangements and Counteracts Severe Cyanide Poisoning. FASEB BioAdv 1(2):81-92, 2019.

 M Lavan, GT Knipp. Effects of Dendrimer-Like Biopolymers on Physical Stability of Amorphous Solid Dispersions and Drug Permeability across Caco-2 Cell Monolayers. AAPS PharmSciTech 19(6):2459-2471, 2018.

NH Sulimai, JC Ko, Y Jones-Hall, et al. Pharmacokinetic and Histopathological Evaluation of 25% Poloxamer as a Slow Release Carrier for Morphine in a Rat Model. Front. Vet. Sci. 5:Article 9, 2018.

C Kulczar, KL Lubin, S Lefebvre, DW Miller, GT Knipp.  Development of a Direct Contact Astrocyte-hCMEC/D3 Blood-Brain Barrier Coculture Model. J. Pharm. Pharmacol. 69(12):1684-1696, 2017.

LR Eichstadt, LA Corriveau, GE Moore, GT Knipp, et al. Absorption of Transdermal Fluoxetine Compounded in a Lipoderm Base Compared to Oral Fluoxetine in Client-Owned Cats. Int J Pharm Compd 21(3):242-246, 2017.

RP Gala, C Popescu, GT Knipp*, et al. Physicochemical and Preclinical Evaluation of a Novel Buccal Measles Vaccine. AAPS PharmSciTech 18(2):1-10, 2017.

Lavan, Monika; Byrn, Stephen R.; Knipp, G.T. Pediatric Formulations: Knowledge Gaps Limiting the Expedited Preclinical to Clinical Translation in ChildrenAAPS PharmSciTech (2019) 20(2):73 (EPub December 2018).

Morningstar, Jordan; Lee, Jangwoen; Hendry-Hofer, Tara; Witeof, Alyssa; Lyle, Tiffany; Knipp, Greg; McCrae, Calum A.; Boss, Gerry R.; Peterson, Randall T.; Davisson, Vincent J.; Gerszten, Robert E.; Bebarta, Vikhyat S.; Mahon, Sara; Brenner, Matt; Nath, Anjali K. Intramuscular Administration of Hexachloroplatinate Reverses Cyanide-Induced Metabolic Derangements and Counteracts Severe Cyanide Poisoning. FASEB BioAdv (Epub October 8, 2018; https://doi.org/10.1096/fba.1024).

Lavan, Monika; Knipp, Gregory T. Effects of Dendrimer-Like Biopolymers on Physical Stability of Amorphous Solid Dispersions and Drug Permeability across Caco-2 Cell Monolayers. AAPS PharmSciTech (2018) 19(6):2459-2471.

Sulimai, Nural H.; Ko, Jeff C.; Jones-Hall, Yava L.; Weng, Hsin-Yi; Deng, Meng; Breur, Gert J.; Knipp, Gregory T. Pharmacokinetic and Histopathological Evaluation of 25% Poloxamer as a Slow Release Carrier for Morphine in a Rat Model. Frontiers in Veterinary Science. (2018) 5: Article 9.

C. Kulczar, K.L. Lubin, S. Lefebvre, D.W. Miller, and G.T. Knipp.  Development of a Direct Contact Astrocyte-hCMEC/D3 Blood-Brain Barrier Coculture Model. J. Pharm. Pharmacol. 69(12):1684-1696 (2017).

L.R. Eichstadt, L.A. Corriveau, G.E. Moore, G.T. Knipp, B. Cooper, and W.E. Gwin. Absorption of Transdermal Fluoxetine Compounded in a Lipoderm Base Compared to Oral Fluoxetine in Client-Owned Cats. Int J Pharm Compd 21(3):242-246. (2017).

R.P. Gala, C. Popescu, G.T. Knipp*, R.R. McCain, R.V. Ubale, R. Addo, T. Bhowmik, C.D. Kulczar, and M.J. D’Souza*, Physicochemical and Preclinical Evaluation of a Novel Buccal Measles Vaccine. AAPS PharmSciTech [Pediatric Drug Development and Dosage Form Theme Issue] 18(2):1-10 (2017).

R.P. Gala, C. Popescu, G.T. Knipp*, R.R. McCain, R.V. Ubale, R. Addo, T. Bhowmik, C.D. Kulczar, and M.J. D’Souza*, Physicochemical and Preclinical Evaluation of a Novel Buccal Measles Vaccine. AAPS PharmSciTech [Pediatric Drug Development and Dosage Form Theme Issue] 1-10 (EPub June 29, 2016; Shared: http://rdcu.be/ndT7).

J. Kim, Y.L. Jones, R. Wei, J. Myers, Y. Qi, G.T. Knipp, and W. Liu. Association between hTERT rs2736100 polymorphism and sensitivity to anti-cancer agents. Front. Genetics. 4 (Article 162):1-6 (2013).

W.J. Roth, C.B. Kissinger, R.R. McCain, B.R. Cooper, J.N. Marchant-Forde, R.C. Vreeman, S. Hannou, and G.T. Knipp.  Assessment of Juvenile Pigs to Serve as Human Pediatric Surrogates for Preclinical Formulation Pharmacokinetic Testing. AAPS J. [Theme Issue: Challenges and Opportunities in Pediatric Drug Development] 15 (3):763-774 (2013; EPub: April 18, 2013).

Editorial: Perspectives on Pediatric Drug Development. Roth, WJ, Sage, DP, Kulczar, C, Liu, W, and Knipp, GT. Revista Mexicana De Ciencias Farmaceuticas 2012; 43 (3):5-6.

Comparative Pharmacokinetic Studies of Immediate and Modified Release Formulations of Glipizide in Pigs and Dogs. Kulkarni, R, Yumibe, N, Wang, Z, Zhang, X, Tang, CC, Ruterbories, K, Cox, A, McCain, R, and Knipp, GT. J. Pharm. Sci. 2012; 101 (11): 4327-4336, 2012. Epub 19 August 2012. 

The Effects of Intra-Laboratory Modifications to Media Composition and Cell Source on the Expression of Pharmaceutically Relevant Transporters and Metabolizing Genes in the Caco-2 Cell Line. Roth WJ, Lindley, DJ, Carl, SM, and Knipp, GTJ. Pharm. Sci. 11 July 2012; 101 (10): 3962-3978. Epub 11 July 2012. 

The Effects of Media on Pharmaceutically Relevant Transporters in the Human HT-29 Adenocarcinoma Cell Line: Does Culture Media Need to be Controlled? Lindley, DJ, Roth, WJ, Carl, SM, and Knipp, GT. J. Pharm. Sci. 2012; 101 (4): 1616-1630.

Plasma Cortisol and Noradrenalin Concentrations in Pigs: Automated Sampling of Freely Moving Pigs Housed in the PigTurn® Versus Manually Sampled and Restrained Pigs. Marchant-Forde, JN, Matthews, DL, Poletto, R, McCain, RR, Mann, DD, McGraw, RT,  Hampsch, J, Peters, S, Knipp, GT, and Kissinger, CB. Anim. Welfare 2012; 21: 197-205.

Assessing the Performance of Amorphous Solid Dispersions. Newman, A, Knipp, G, and Zografi, G. J. Pharm. Sci. 2012: 101: 1355–1377.

Summary of the national institute of child health and human development-best pharmaceuticals for children act pediatric formulation initiatives workshop-pediatric biopharmaceutics classification system working group. Abdel-Rahman SM, Amidon GL, Kaul A, Lukacova V, Vinks AA, Knipp GT.  Members of the BCS Task Force. Clin Ther. 2012 Nov;34(11):S11-24. doi:10.1016/j.clinthera.2012.09.014.

"ABC and SLC Transporter Expression and Proton Oligopeptide Transporter (POT) Mediated Permeation across the Human Blood-Brain Barrier Cell Line, hCMEC/D3". Carl SM, Lindley DJ, Das D, Couraud PO, Weksler BB, Romero I, Mowery SA, Knipp GT. Mol Pharm. 2012 Nov 6. [Epub ahead of print] No abstract available.

The Evaluation of Peptide/Histidine Transporter 1 (PHT1) Function: Uptake Kinetics Utilizing a COS-7 Stably Transfected Cell Line.  Lindley DJ, Carl SM, Mowery S, Knipp GT. Revista Mexicana De Ciencia Farmaceuticas, octubre-diciembre 2011; 42(4);57-65.

ABC and SLC transporter expression and pot substrate characterization across the human CMEC/D3 blood-brain barrier cell line. Carl SM, Lindley DJ, Couraud PO, Weksler BB, Romero I, Mowery SA, Knipp GT. Mol Pharm. 2010 Aug 2;7(4):1057-68.

The effects of excipients on transporter mediated absorption. Goole J, Lindley DJ, Roth W, Carl SM, Amighi K, Kauffmann JM, Knipp GT. Int J Pharm. 2010 Jun 30;393(1-2):17-31. Epub 2010 Apr 24. 

Book Chapters:

Invited Chapters

1.    D.J. Lindley, S.M. Carl, D.R. Herrera-Ruiz, L.-F. Pan, L.B. Ward, J.M.E. Goole, O.S. Gudmundsson, and G.T. Knipp. Chapter 18: Drug Transporters and Their Role in Absorption and Disposition of Peptides and Peptide Based Pharmaceuticals. In Oral Bioavailability: Basic Principles, Advanced Concepts and Application. Eds. M. Hu and X. Li. In the Wiley Series on Drug Discovery and Development, Series Ed. B. Wang, John Wiley & Sons, New York, NY. pp. 291-308 (2011).

2.   S.M. Carl, D.J. Lindley, G.T. Knipp, K.R. Morris, E. Oliver, G.W. Becker and R.A. Arnold. Biotechnology Drug Product Development. In Pharmaceutical Manufacturing Handbook, Editor S.H. Gad, John Wiley & Sons, New York, NY, pp. 1-32 (2008). [DOI: 10.1002/9780470259818.ch1; Republished in a Wiley Special Edition Series “Pharmaceutical Sciences Encyclopedia: Drug Discovery, Development, and Manufacturing.” DOI: 10.1002/9780470571224.pse340 1-26 (2010)]

3.   E. Oliver, S.M. Carl, K.R. Morris, G.W. Becker and G.T. Knipp. Regulatory Considerations in the Approval of Follow-On Protein Drug Products. In Pharmaceutical Manufacturing Handbook, Editor S.H. Gad, John Wiley & Sons, New York, NY, pp. 33-57 (2008). [DOI: 10.1002/9780470259818.ch2; Republished in a Wiley Special Edition Series entitled “Pharmaceutical Sciences Encyclopedia: Drug Discovery, Development, and Manufacturing.” 1–32 (2010)] 

4.    S.M. Carl, D.J. Lindley, G.T. Knipp, K.R. Morris, E. Oliver, G.W. Becker and R.A. Arnold, Biotechnology Drug Product Development. In Pharmaceutical Manufacturing Handbook, Editor S.H. Gad, John Wiley & Sons, New York, NY, pp. 1-32 (2008).

5.    E. Oliver, S.M. Carl, K.R. Morris, G.W. Becker and G.T. Knipp. Regulatory Considerations in the Approval of Follow On Protein Drug Products. In Pharmaceutical Manufacturing Handbook, Editor S.H. Gad, John Wiley & Sons, New York, NY, pp. 33-57 (2008).

6.    R.K. Bhardwaj, D.R. Herrera-Ruiz, Y. Xu, S.M. Carl, T.J. Cook, N. Vorsa, and G.T. Knipp. Chapter 7: Intestinal Transporters in Drug Absorption. In Biopharmaceutics Applications in Drug Development. Editors R. Krishna and L. Yu, Kluwer Press, NY, pp. 175-261 (2008).

Edited Textbook Chapters

Martin’s Physical Pharmacy and Pharmaceutical Sciences, Fifth Edition. Editor Patrick J. Sinko. Lippincott, Williams & Wilkins, Baltimore, MD, (2006).

1.    G.T. Knipp and K.R. Morris, Chapter 2: States of Matter.

2.    H. Morelos, D. Herrera-Ruiz, and G.T. Knipp, Chapter 3: Thermodynamics.

3.    G.T. Knipp, H. Morelos and D. Herrera-Ruiz, Chapter 4: Physical Properties of Drug Molecules.

Refereed Abstracts 

  1. N. Yumibe, R. Kulkarni, Z. Wang, X. Zhang, K. Ruterbories, A. Cox, R. Ajamie, C.C. Tang, G. Knipp, Robin McCain. Comparative Pharmacokinetic Studies of Immediate and Modified Release Formulations of Glipizide in Pigs and Dogs. 2011 AAPS Indiana/Ohio Discussion Group-Pharma Industry Challenges/Perspectives Symposium, Indianapolis, IN. (2011).
  2. W.J. Roth, C.B. Kissinger, S. Hannou, B.R. Cooper, R.R. McCain,  R. Vreeman, and G.T. Knipp. Development and Testing of Novel Pediatric Formulation of Rifampicin for the Treatment of Tuberculosis (TB) in Infants and Young Children. 2011 AAPS Indiana/Ohio Discussion Group-Pharma Industry Challenges/Perspectives Symposium, Indianapolis, IN. (2011). Best Poster Award

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