BioHighland Consulting LLC

BioHighland Consulting LLCBioHighland Consulting LLCBioHighland Consulting LLC
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BioHighland Consulting LLC

BioHighland Consulting LLCBioHighland Consulting LLCBioHighland Consulting LLC
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Providing expert advice for Biotech or Pharmaceutical R&D

Providing expert advice for Biotech or Pharmaceutical R&DProviding expert advice for Biotech or Pharmaceutical R&DProviding expert advice for Biotech or Pharmaceutical R&D

Providing expert advice for Biotech or Pharmaceutical R&D

Providing expert advice for Biotech or Pharmaceutical R&DProviding expert advice for Biotech or Pharmaceutical R&DProviding expert advice for Biotech or Pharmaceutical R&D

About BioHighland Consulting LLC

Our Expertise

BioHighland Consulting LLC provides scientific, technical and strategic consulting to the biotech and pharmaceutical business at all stages of drug discovery and development 

Peter R Young

Peter R Young is a former biotech executive with hands on experience in multiple platforms (small molecules, peptide and antibodies), stages (target validation, candidate selection, preclinical development, early clinical/ translational studies) and therapeutic areas (cancer, autoimmune, metabolic, cardiovascular, renal, pulmonary, CNS, anti-viral) as evidenced by multiple regulatory drug filings, publications and patents.

Our Approach

At BioHighland Consulting LLC, specific consulting projects are discussed and tailored to each client's needs and budget

Areas of Expertise

Multiple Therapeutics Areas

Hands-on knowledge of underlying biology, in vitro/in vivo models for compound progression, biomarker discovery and clinical designs for testing new drugs. 

Examples include Neurodegeneration, Oncology, Immunological Diseases, Hematopoiesis/Renal, Infectious Disease, Cardiovascular/Metabolic and Pulmonary

Targets and therapeutics modalities

Discovery and characterization of targets

Design and Implementation of drug  discovery screens

Discovery and implementation of biomarkers in clinical trials.

Strategic and Project Management

Planning and management of research project priorities and timelines

Incorporation of patent strategy into research priorities

Presentations and Scientific Writing

Review and editing of non-clinical sections of  IBs, INDs, orphan drug applications and  translational components of clinical protocols and CSRs  (submitted multiple examples to Regulatory bodies)

Review and editing of papers for submission to journals (Published > 120 papers in peer reviewed journals)

Review and editing of technical sections of patent applications (Inventor on > 40 issued US patents)

Review and editing of presentations for multiple audiences

Due Diligence

Conduct of both in-and out-licensing opportunities in multiple therapeutic areas

Therapeutic Area Experience: Neurodegeneration

Nonclinical

Research to support testing of PIKfyve inhibitor in ALS

Clinical

Design, IND submission and conduct of POC Phase 2 biomarker study of apilimod dimesylate (PIKfyve Inhibitor) in a genetic subset of ALS subjects (NCT05163886; https://clinicaltrials.gov/study/NCT05163886?term=NCT05163886&rank=1 ).

Wrote and obtained US and European Orphan drug status for apilimod dimesylate for ALS

Literature

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Patents and Patent Applications

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Therapeutic Area Experience: Oncology

Nonclinical

Small molecule discovery and research directed at  kinases (PIKfyve,  BTK, mTOR) and epigenetic (HDACs, BET proteins) targets 

Discovery and validation of PD biomarkers to support clinical trials. 

Clinical

Design and conduct of Phase I clinical trial of HSP90 inhibitor for AML (LAM-003: NCT03426605; https://clinicaltrials.gov/study/NCT03426605?intr=LAM-003&rank=1).

Support of Phase 2 clinical study of PIKfyve inhibitor in Non-Hodgkin’s lymphoma (LAM-002A: NCT02594384; https://clinicaltrials.gov/study/NCT02594384?intr=LAM-002A&rank=2

Measurement of HDAC inhibitor target engagement biomarkers in Phase I studies to support dose selection (abexinostat: NCT00473577; https://clinicaltrials.gov/study/NCT00473577?term=CRA-024781&rank=1)

Product

Ibrutinib/Imbruvica  for hematopoietic cancers (approved for MCL, SLL/CLL, WM, MZL cancer) 

Literature

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Patents

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Therapeutic Area Experience: Immunological Diseases

Nonclinical

Small molecule programs targeting cytokines/chemokines  (IL-1, IL-5, IL-8), kinases (p38MAPK, BTK), epigenetics (BET) and proteases (cathepsin S)  

Identification and implementation of clinical biomarkers. 

Clinical

Measurement of cathepsin S inhibitor (CRA-028129) target engagement biomarkers in Phase I study to support dose selection 

Product

Mepolizumab/Nucala for severe asthma and eosinophilic granulomatosis.

Literature

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Patents

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Therapeutic Area Experience: Hematopoiesis/Renal

Nonclinical

Programs targeting EPO, TPO and G-CSF mimetics (small molecule, peptide and/or agonist antibody).

Translational studies to support clinical programs (peginesatide, Phase 3; NCT00372489)

Products

Eltrombopag (Promacta); Peginesatide (Omontys). 

Literature

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Patents

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Therapeutic Area experience: Infectious Disease

Nonclinical

Programs to identify and/or evaluate small molecules targeting COVID-19 (PIKfyve) and Hepatitis C (Reverse transcriptase, protease, N5A).

Clinical

Design and conduct of POC Phase 2 trial of PIKfyve inhibitor for COVID-19 (LAM-002A: NCT04446377; https://clinicaltrials.gov/study/NCT04446377?intr=LAM-002A&rank=3

Patent Application

 Young PR, Landrette S, Spirli C, Fandrick K, Gunel M. “Antiviral Compositions and Methods.” US20240189317

Therapeutic Area Experience: Cardiovascular/Metabolic

Nonclinical

Programs in dyslipidemia and atherosclerosis targeting PPARalpha, FXR, BET, ACC and DGAT.  

Preclinical studies to support clinical program in atherosclerosis (apabetalone (RVX-208); BET inhibitor) and role of cytokines in stroke.  

Literature

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Patents

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Therapeutic Area Experience: Pulmonary

Nonclinical

Discovery of  mTOR/DRR pathway that led to multiple uses including pulmonary applications

Program to discover Monoclonal Antibody to IL-5 for treating asthma

Clinical

Design and implementation of translational measures to support clinical studies in peripheral hypertension and bronchiolitis obliterans of inhaled mTOR inhibitor (sirolimus)

Wrote and obtained orphan drug application for inhaled mTOR inhibitor in select lung diseases

Product

Mepolizumab/Nucala for severe asthma 

Literature

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Patent

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Experience: Targets and Biomarkers

Summary

Discovered and/or characterized multiple novel genes and gene products  (examples include cytokines, cytokine receptors, protein kinases, protein phosphatases, transcription factors, epigenetic regulators, proteases, DNA binders).. 

Discovered, tested  and implemented multiple biomarkers in preclinical  animal models and clinical trials for target engagement,  proof of mechanism and efficacy (examples include HDAC inhibitor, Cathepsin S inhibitor, BET inhibitor, PIKfyve inhibitor) 

Literature

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Patents

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Publications: Neurodegeneration

Peer Reviewed Literature


  1. Babu S, Nicholson KA, Rothstein JD, Swenson A, Sampognaro PJ, Pant P, Macklin EA, Spruill S, Paganoni S, Gendron TF, Prudencio M, Petrucelli L, Nix D, Landrette S, Nkrumah E, Fandrick K, Edwards J, Young PR. Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial. Brain. 2024 Sep 3;147(9):2998-3008.. doi.org/10.1093/brain/awae109
  2. Young PR, Bedell BJ, DeDuck K. AIT-101 Improves Functional Deficits in a Human TDP-43 Animal Model of ALS. Conference Int. Motor Neuron Dis Annual Meeting, Basel, Switzerland. 2023. doi: 10.13140/RG.2.2.18859.76327


Patents


  1. Lichenstein, H., Landrette, S., Young, P.R., Rothberg, J.M. “Combination Therapy with Apilimod and glutamatergic agents”, US Patent 11,957,688 B2, April 16th, 2024
  2. Lichenstein, H., Landrette, S., Young, P.R., Rothberg, J.M. “Combination Therapy with Apilimod and glutamatergic agents”, US Patent 11,439,649 B2, Sept 13, 2022
  3. Lichenstein, H., Landrette, S., Young, Peter R., Rothberg J.M. “Combination Therapy with Apilimod and Glutamatergic Agents”. US Patent No. US 10,751,345 B2, Aug 25th, 2020


Patent Applications


  1.  Young PR, Spirli C. “PIKfyve Inhibitor Combination Therapy”. WO 2024/191947 A1, Sept 19th, 2024
  2. Young PR, Spirli C. “Apilimod Combination Therapy”. WO 2024/118515 A1, June 6th, 2024
  3.  Young PR, Spirli C. “Apilimod Combination Therapy”. WO 2024/107448 A1  May 23rd, 2024
  4.  Young PR. “Aplimod Compositions and Methods of Use”. Jan 25th, 2024. WO 2024/0024332 A1.
  5.  Young PR, Spirli C. “Apilimod Combination Therapy”.  WO 2024/015281 A1, Jan 18th, 2024
  6.  Young PR, Spirli C. “Apilimod Combination Therapy”. WO 2024/015286 A1, Jan 18th, 2024

Publications: Oncology

Peer Reviewed Literature


  1. Beeharry N, Landrette S, Gayle S, Hernandez M, Grotzke JE, Young PR, Beckett P, Zhang X, Carter BZ, Andreeff M, Halene S, Xu T, Rothberg J, Lichenstein H. LAM-003, a new drug for treatment of tyrosine kinase inhibitor-resistant FLT3-ITD-positive AML. Blood Adv. 2019 Nov 26;3(22):3661-3673. doi: 10.1182/bloodadvances.2019001068. https://pmc.ncbi.nlm.nih.gov/articles/PMC6880894/
  2. Rutherford, S.C., Harb, W.A., Diefenbach, C.S., Ansell, S.M., Nastoupil, L.J., Abramson, J.S., Lakhani, N., Schreeder, M.T., Sher9, S.,, Patel-Donnelly, D., Aboulafia, D.M, Fuchs, C., Nix, D., Landrette, S., Graham, P., King, L., Young, P.R., Miller, L.L., Lichenstein, H., Cohen, J.B. (2020)  Results of a completed phase I study of LAM-002 (apilimod dimesylate), a first-in-class phosphatidylinositol-3-phosphate 5 kinase (PIKfyve) inhibitor, administered as monotherapy or with rituximab or atezolizumab to patients with previously treated follicular lymphoma or other B-cell cancers. J Clin Oncol. 38 Suppl 15.https://doi.org/10.1200/JCO.2020.38.15_suppl.8017
  3. Kharenko OA, Patel RG, Brown SD, Calosing C, White A, Lakshminarasimhan D, Suto RK, Duffy BC, Kitchen DB, McLure KG, Hansen HC, van der Horst EH, Young PR. Design and Characterization of Novel Covalent Bromodomain and Extra-Terminal Domain (BET) Inhibitors Targeting a Methionine. J Med Chem. 2018 Sep 27;61(18):8202-8211. doi: 10.1021/acs.jmedchem.8b00666. https://pubmed.ncbi.nlm.nih.gov/30165024/
  4. Kharenko OA, Gesner EM, Patel RG, Norek K, White A, Fontano E, Suto RK, Young PR, McLure KG, Hansen HC. RVX-297- a novel BD2 selective inhibitor of BET bromodomains. Biochem Biophys Res Commun. 2016 Aug 12;477(1):62-67. doi: 10.1016/j.bbrc.2016.06.021
  5. Campeau E, Jahagirdar R, Wu J, Gesner EM, Kharenko O, Yu R, Attwell S, Hansen HC, Wagner GS, McLure KG, Young PR. RVX-2135 is a novel, orally bioavailable epigenetic BET inhibitor that synergizes with cytarabine and idarubicin to inhibit proliferation of acute myeloid leukemia cells. Cancer Res. 2013  73 (8_Supplement): LB-92. Doi: 10.1158/1538-7445.AM2013-LB-92
  6. Pan Z, Scheerens H, Li SJ, Schultz BE, Sprengeler PA, Burrill LC, Mendonca RV, Sweeney MD, Scott KC, Grothaus PG, Jeffery DA, Spoerke JM, Honigberg LA, Young PR, Dalrymple SA, Palmer JT. Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem. 2007 Jan;2(1):58-61. doi: 10.1002/cmdc.200600221
  7. Buggy JJ, Cao ZA, Bass KE, Verner E, Balasubramanian S, Liu L, Schultz BE, Young PR, Dalrymple SA. CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther. 2006 May;5(5):1309-17. doi: 10.1158/1535-7163.MCT-05-0442. 10.1158/1535-7163.MCT-05-0442
  8. Cao ZA, Bass KE, Balasubramanian S, Liu L, Schultz B, Verner E, Dai Y, Molina RA, Davis JR, Misialek S, Sendzik M, Orr CJ, Leung L, Callan O, Young P, Dalrymple SA, Buggy JJ. CRA-026440: a potent, broad-spectrum, hydroxamic histone deacetylase inhibitor with antiproliferative and antiangiogenic activity in vitro and in vivo. Mol Cancer Ther. 2006 Jul;5(7):1693-701. doi:10.1158/1535-7163.MCT-06-0042
  9. Spencer JR, Sendzik M, Oeh J, Sabbatini P, Dalrymple SA, Magill C, Kim HM, Zhang P, Squires N, Moss KG, Sukbuntherng J, Graupe D, Eksterowicz J, Young PR, Myers AG, Green MJ. Evaluation of antitumor properties of novel saframycin analogs in vitro and in vivo. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4884-8. doi: 10.1016/j.bmcl.2006.06.085
  10. Cafferkey R, McLaughlin MM, Young PR, Johnson RK, Livi GP. Yeast TOR (DRR) proteins: amino-acid sequence alignment and identification of structural motifs. Gene. 1994 Apr 8;141(1):133-6. doi: 10.1016/0378-1119(94)90141-4
  11. Cafferkey R, Young PR, McLaughlin MM, Bergsma DJ, Koltin Y, Sathe GM, Faucette L, Eng WK, Johnson RK, Livi GP. Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol Cell Biol. 1993 Oct;13(10):6012-23. doi: 10.1128/mcb.13.10.6012-6023.1993


Patents


  1. Quinn, J.F., Duffy, B.C., Liu, S., Wang, R., Jiang, M.X., Martin, G.S., Wagner, G.S., Young, P.R. “Bicyclic Bromodomain Inhibitors”. US Patent No. 11,446,306 B2, Sept 20th, 2022.
  2. Liu, S., Quinn, J.F., Duffy, B.C., Wang, R., Jiang, M.X., Martin, G.S., Zhao, H., Ellis, M., Wagner, G.S., Young, P.R. “Substituted Bicyclic Compounds as Bromodomain, Inhibitors”. US Patent No. 11,026,926 B2, June 8th, 2021
  3. Quinn, J.F., Duffy, B.C., Liu, S., Wang, R., Jiang, M.X., Martin, G.S., Wagner, G.S., Young, P.R. “Bicyclic Bromodomain Inhibitors”. US Patent No. 10,772,892, Sept 15th, 2020.
  4. Quinn, J.F., Duffy, B.C., Liu, S., Wang, R., Jiang, M.X., Martin, G.S., Wagner, G.S., Young, P.R. “Bicyclic Bromodomain Inhibitors”. US Patent No. 10,363,257, July 30, 2019.
  5. Kharenko, O., Young, P.R., Brown, S.D., Duffy, B.C., Liu, S., Guzzo, P. “Inhibitors of Bromodomains”. US Patent No. 10,231,953, March 19, 2019
  6.  Liu, S., Quinn, J.F., Duffy, B.C., Wang, R., Jiang, M.X., Martin, G.S., Zhao, H., Ellis, M., Wagner, G.S., Young, P.R. “Substituted Bicyclic Compounds as Bromodomain Inhibitors”. US Patent No. 10,226,451, March 12, 2019
  7. Liu, S., Quinn, J.F., Duffy, B.C., Wang, R., Jiang, M.X., Martin, G.S., Zhao, H., Ellis, M., Wagner, G.S., Young, P.R. “Substituted Bicyclic Compounds as Bromodomain Inhibitors”. US Patent No. 10,166,215, Jan 1, 2019
  8. Quinn, J.F., Duffy, B.C., Liu, S., Wang, R., Jiang, M.X., Martin, G.S., Wagner, G.S., Young, P.R. “Bicyclic Bromodomain Inhibitors”. US Patent No. 10,010,556, July 3, 2018
  9. Liu, S., Duffy, B.C., Quinn, J.F., Jiang, M.X., Wang, R., Martin, G.S., Zhao, G.S., Zhao, H., Molino, B.F., Young, P.R. “Heterocyclic compounds as Bromodomain Inhibitors”. U.S. Patent No. 9,861,637, Jan 9, 2018.
  10. Fairfax, D.J., Martin, G.S., Quinn, J.F., Duffy, B.C., Wagner, G.S., Young, P.R. “Biaryl derivatives as bromodomain inhibitors”. U.S. Patent No. 9,765,039, Sept 19, 2017
  11. Quinn, J.F., Duffy, B.C., Liu, S., Wang, R., Jiang, M.X., Martin, G.S., Wagner, G.S., Young, P.R. “Bicyclic Bromodomain Inhibitors”. U.S. Patent No. 9,663,520, May 30, 2017
  12. Liu, S., Quinn, J.F., Duffy, B.C., Wang, R., Jiang, M.X., Martin, G.S., Zhao, H., Ellis, M., Wagner, G.S., Young, P.R. “Substituted bicyclic compounds as bromodomain inhibitors.” U.S. Patent No. 9,662,311, May 30, 2017
  13. Liu, S., Quinn, J.F., Duffy, B.C., Wang, R., Jiang, M.X., Martin, G.S., Zhao, H., Ellis, M., Wagner, G.S., Young, P.R. “Substituted bicyclic compounds as bromodomain inhibitors.” U.S. Patent No. 9,636,328, May 2, 2017
  14. Liu, S., Duffy, B.C., Quinn, J.F., Jiang, M.X., Wang, R., Martin, G.S., Zhao, H., Molino, B.F., Young, P.R. “Heterocyclic compounds as bromodomain inhibitors.” U.S. Patent No. 9,598,367, March 21, 2017.
  15. Fairfax, D.J., Duffy, B.C., Martin, G.S., Quinn, J.F., Liu, S., Wagner, G.S. Young, P.R. “Cyclic Amines as Bromodomain Inhibitors”. US Patent No. 9,278,940, March 8, 2016.
  16. Liu, S., Duffy, B.C. Quinn, J.F., Jiang, M.X., Wang, R., Martin, G.S., Zhao, H., Molino, B.F., Young, P.R. “Heterocyclic Compounds as Bromodomain Inhibitors.”  U.S. Patent No. 9,271,978. March 1, 2016.
  17. Fairfax, D.J., Duffy, B.C., Martin, G.S., Quinn, J.F., Liu, S., Wagner, G.S. Young, P.R. “Cyclic Amines as Bromodomain Inhibitors”. US Patent No. 9,073,878, July 7, 2015.

Publications: Immunological Diseases

Peer Reviewed Literature


  1. Jahagirdar R, Attwell S, Marusic S, Bendele A, Shenoy N, McLure KG, Gilham D, Norek K, Hansen HC, Yu R, Tobin J, Wagner GS, Young PR, Wong NCW, Kulikowski E. RVX-297, a BET Bromodomain Inhibitor, Has Therapeutic Effects in Preclinical Models of Acute Inflammation and Autoimmune Disease. Mol Pharmacol. 2017 Dec;92(6):694-706. doi: 10.1124/mol.117.110379
  2. Pan Z, Scheerens H, Li SJ, Schultz BE, Sprengeler PA, Burrill LC, Mendonca RV, Sweeney MD, Scott KC, Grothaus PG, Jeffery DA, Spoerke JM, Honigberg LA, Young PR, Dalrymple SA, Palmer JT. Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem. 2007 Jan;2(1):58-61. doi: 10.1002/cmdc.200600221
  3. White JR, Lee JM, Young PR, Hertzberg RP, Jurewicz AJ, Chaikin MA, Widdowson K, Foley JJ, Martin LD, Griswold DE, Sarau HM. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem. 1998 Apr 24;273(17):10095-8. doi: 10.1074/jbc.273.17.10095
  4. Kumar S, Tzimas MN, Griswold DE, Young PR. Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli. Biochem Biophys Res Commun. 1997 Jun 27;235(3):474-8. doi: 10.1006/bbrc.1997.6810
  5. Salmon RA, Foltz IN, Young PR, Schrader JW. The p38 mitogen-activated protein kinase is activated by ligation of the T or B lymphocyte antigen receptors, Fas or CD40, but suppression of kinase activity does not inhibit apoptosis induced by antigen receptors. J Immunol. 1997 Dec 1;159(11):5309-17. Doi: 10.4049/jimmunol.159.11.5309
  6. Sutherland CL, Heath AW, Pelech SL, Young PR, Gold MR. Differential activation of the ERK, JNK, and p38 mitogen-activated protein kinases by CD40 and the B cell antigen receptor. J Immunol. 1996 Oct 15;157(8):3381-90. Doi: 10.4049/jimmunol.157.8.3381
  7. Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R, et al. Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins. J Biol Chem. 1995 Apr 21;270(16):9459-71. doi: 10.1074/jbc.270.16.9459
  8. Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR, Lee JC. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett. 1995 May 8;364(2):229-33. doi: 10.1016/0014-5793(95)00357-f
  9. Chabot-Fletcher M, Breton J, Lee J, Young P, Griswold DE. Interleukin-8 production is regulated by protein kinase C in human keratinocytes. J Invest Dermatol. 1994 Oct;103(4):509-15. doi: 10.1111/1523-1747.ep12395658
  10. Morton TA, Bennett DB, Appelbaum ER, Cusimano DM, Johanson KO, Matico RE, Young PR, Doyle M, Chaiken IM. Analysis of the interaction between human interleukin-5 and the soluble domain of its receptor using a surface plasmon resonance biosensor. J Mol Recognit. 1994 Mar;7(1):47-55. doi: 10.1002/jmr.300070107
  11. Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, Strickler JE, McLaughlin MM, Siemens IR, Fisher SM, Livi GP, White JR, Adams JL, Young PR. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994 Dec 22-29;372(6508):739-46. doi: 10.1038/372739a0
  12. Hazuda DJ, Strickler J, Kueppers F, Simon PL, Young PR. Processing of precursor interleukin 1 beta and inflammatory disease. J Biol Chem. 1990 Apr 15;265(11):6318-22. Doi: 10.1016/S0021-9258(19)39328-7
  13. Hazuda DJ, Lee JC, Young PR. The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin 1 alpha and interleukin 1 beta. J Biol Chem. 1988 Jun 15;263(17):8473-9. Doi: 10.1016/S0021-9258(18)68502-3
  14. Meyers CA, Johanson KO, Miles LM, McDevitt PJ, Simon PL, Webb RL, Chen MJ, Holskin BP, Lillquist JS, Young PR. Purification and characterization of human recombinant interleukin-1 beta. J Biol Chem. 1987 Aug 15;262(23):11176-81. Doi: 10.1016/S0021-9258(18)60941-X


Reviews


  1. Young PR. Pharmacological modulation of cytokine action and production through signaling pathways. Cytokine Growth Factor Rev. 1998 Sep-Dec;9(3-4):239-57. Doi: 10.1016/s1359-6101(98)00011-2
  2. Lee, JC., Kumar, S, Young, PR. Regulation of Inflammatory Cytokine Biosynthesis: Discovery of a Low Molecular Weight Inhibitor and its Molecular Target. In "Cell Cycle Regulation" Ed. Ruffolo Jr., R.R., Poste, G. and Metcalf, B.W. Harwood Academic Publishers 1997  pp53-66.
  3. Lee JC, Young PR. Role of CSB/p38/RK stress response kinase in LPS and cytokine signaling mechanisms. J Leukoc Biol. 1996 Feb;59(2):152-7. doi: 10.1002/jlb.59.2.152
  4. Lee JC, Prabhakar U, Griswold DE, Dunnington D, Young PR, Badger A. Low-molecular-weight TNF biosynthesis inhibitors: strategies and prospectives. Circ Shock. 1994 Nov;44(3):97-103.
  5. Lee JC, Badger AM, Griswold DE, Dunnington D, Truneh A, Votta B, White JR, Young PR, Bender PE. Bicyclic imidazoles as a novel class of cytokine biosynthesis inhibitors. Ann N Y Acad Sci. 1993 Nov 30;696:149-70. Doi: 10.1111/j.1749-6632.1993.tb17149.x


Patents


  1. Kumar, S., Livi, G.P., McLaughlin; M.M., Young, P.R. “Methods of the identification of pharmaceutically active compounds”. US Patent No. 6,218,136, Apr. 2001.
  2. Lee, J.C., Adams, J.L., Gallagher, T.F., Green, D.W., Heys, R.R., McDonnell, P.C. McNulty, D.E., Strickler, J.E., Young, P.R. “Polynucleotides encoding cytokine suppressive anti-inflammatory drug binding proteins”. U.S. Patent No. 5,955,366, Sept.1999.
  3. Lee, J.C., Adams, J.L., Gallagher, T.F., Green, D.W., Heys, R.R., McDonnell, P.C. McNulty, D.E., Strickler, J.E., Young, P.R. Screening Methods for CSAID Binding Proteins. U.S. Patent No. 5,871,934, Feb. 1999.
  4. McDonnell, P.C., Young, P.R. "Drug Binding protein". U.S. Patent No. 5,869,043, Feb. 1999.
  5. Lee, J.C., Adams, J.L., Gallagher, T.F., Green, D.W., Heys, R.R., McDonnell, P.C. McNulty, D.E., Strickler, J.E., Young, P.R. Cytokine Suppressive Anti-Inflammatory Drug Binding Protein. U.S. Patent No. 5,783,664, July 1998.
  6. Browne, M.J., Young, P.R., Shatzman, A.R., Murphy, K.E., Chapman, C.G., Clinkenbeard, H.E.  Therapeutic Uses of Fusion Proteins between mutant IL 4/IL13 Antagonists and Immunoglobulins. U.S. Patent No. 5,783,181, July 1998.
  7. Lee, J.C., Adams, J.L., Gallagher, T.F., Green, D.W., Heys, R.R., McDonnell, P.C. McNulty, D.E., Strickler, J.E., Young, P.R. Cytokine Suppressive Anti-Inflammatory Drug Binding Protein. U.S. Patent No. 5,777,097, July 1998

Publications: Hematopoiesis /Renal

Peer Reviewed  Literature


  1. Verma R, Su S, McCrann DJ, Green JM, Leu K, Young PR, Schatz PJ, Silva JC, Stokes MP, Wojchowski DM. RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development. J Exp Med. 2014 Aug 25;211(9):1715-22. doi: 10.1084/jem.20130624
  2. Singh S, Verma R, Pradeep A, Leu K, Mortensen RB, Young PR, Oyasu M, Schatz PJ, Green JM, Wojchowski DM. Dynamic ligand modulation of EPO receptor pools, and dysregulation by polycythemia-associated EPOR alleles. PLoS One. 2012;7(1):e29064. doi: 10.1371/journal.pone.0029064
  3. Green JM, Leu K, Worth A, Mortensen RB, Martinez DK, Schatz PJ, Wojchowski DM, Young PR. Peginesatide and erythropoietin stimulate similar erythropoietin receptor-mediated signal transduction and gene induction events. Exp Hematol. 2012 Jul;40(7):575-87. doi: 0.1016/j.exphem.2012.02.007
  4. Doyle ML, Tian SS, Miller SG, Kessler L, Baker AE, Brigham-Burke MR, Dillon SB, Duffy KJ, Keenan RM, Lehr R, Rosen J, Schneeweis LA, Trill J, Young PR, Luengo JI, Lamb P. Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand. J Biol Chem. 2003 Mar 14;278(11):9426-34. doi: 10.1074/jbc.M209220200
  5. Hensley P, Doyle ML, Myszka DG, Woody RW, Brigham-Burke MR, Erickson-Miller CL, Griffin CA, Jones CS, McNulty DE, O'Brien SP, Amegadzie BY, MacKenzie L, Ryan MD, Young PR. Evaluating energetics of erythropoietin ligand binding to homodimerized receptor extracellular domains. Methods Enzymol. 2000;323:177-207. doi: 10.1016/s0076-6879(00)23367-3
  6. Foltz IN, Lee JC, Young PR, Schrader JW. Hemopoietic growth factors with the exception of interleukin-4 activate the p38 mitogen-activated protein kinase pathway. J Biol Chem. 1997 Feb 7;272(6):3296-301. doi: 10.1074/jbc.272.6.3296


Patents


  1.  Erickson-Miller, C.L., Holmes, S.D., Taylor, A.H., Young, P.R. “Erythropoietin Receptor Antibodies”. U.S. Patent No. 6,998,124, Feb. 2006.
  2. Young, P.R. and Erickson-Miller, C. “Erythropoietin Receptor Antibodies”.  US Patent No. 6,153,190, Nov. 2000. 

Publications: Cardiovascular/Metabolic Disease

Peer Reviewed Literature


  1. Wasiak, S., Gilham, D., Tsujikawa, L.M., Halliday, C., Norek, K., Patel, R.G., McLure, K.G., Young, P.R., Gordon, A., Kulikowski, E., Johansson, J., Sweeney, M., Wong, N.C. (2016) Data on gene and protein expression changes induced by apabetalone (RVX-208) in ex vivo treated human whole blood and primary hepatocytes. Data in Brief, doi:10.1016/j.dib.2016.07.047
  2. Gilham D, Wasiak S, Tsujikawa LM, Halliday C, Norek K, Patel RG, Kulikowski E, Johansson J, Sweeney M, Wong NC, Gordon A, McLure K, Young P. RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease. Atherosclerosis. 2016 Apr;247:48-57. doi: 10.1016/j.atherosclerosis.2016.01.036. Erratum for: Atherosclerosis. 2016 Apr;247:48-57 doi:  10.1016/j.atherosclerosis.2016.05.012
  3. Duffy BC, Liu S, Martin GS, Wang R, Hsia MM, Zhao H, Guo C, Ellis M, Quinn JF, Kharenko OA, Norek K, Gesner EM, Young PR, McLure KG, Wagner GS, Lakshminarasimhan D, White A, Suto RK, Hansen HC, Kitchen DB. Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design. Bioorg Med Chem Lett. 2015 Jul 15;25(14):2818-23. doi: 10.1016/j.bmcl.2015.04.107
  4. Jahagirdar R, Zhang H, Azhar S, Tobin J, Attwell S, Yu R, Wu J, McLure KG, Hansen HC, Wagner GS, Young PR, Srivastava RA, Wong NC, Johansson J. A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice. Atherosclerosis. 2014 Sep;236(1):91-100. doi: 10.1016/j.atherosclerosis.2014.06.008
  5. McLure KG, Gesner EM, Tsujikawa L, Kharenko OA, Attwell S, Campeau E, Wasiak S, Stein A, White A, Fontano E, Suto RK, Wong NC, Wagner GS, Hansen HC, Young PR. RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist. PLoS One. 2013 Dec 31;8(12):e83190. doi: 10.1371/journal.pone.0083190
  6. Kassam A, Miao B, Young PR, Mukherjee R. Retinoid X receptor (RXR) agonist-induced antagonism of farnesoid X receptor (FXR) activity due to absence of coactivator recruitment and decreased DNA binding. J Biol Chem. 2003 Mar 21;278(12):10028-32. doi: 10.1074/jbc.M208312200
  7. Liu PC, Huber R, Stow MD, Schlingmann KL, Collier P, Liao B, Link J, Burn TC, Hollis G, Young PR, Mukherjee R. Induction of endogenous genes by peroxisome proliferator activated receptor alpha ligands in a human kidney cell line and in vivo. J Steroid Biochem Mol Biol. 2003 May;85(1):71-9. doi: 10.1016/s0960-0760(03)00135-3
  8. Miao B, Sun S, Santomenna LD, Zhang JH, Young P, Mukherjee R. Ligand-induced coactivator recruitment to peroxisome proliferator-activated receptor alpha characterized by fluorescence resonance energy transfer. Methods Enzymol. 2002;357:180-8. doi: 10.1016/s0076-6879(02)57677-1
  9. Mukherjee R, Sun S, Santomenna L, Miao B, Walton H, Liao B, Locke K, Zhang JH, Nguyen SH, Zhang LT, Murphy K, Ross HO, Xia MX, Teleha C, Chen SY, Selling B, Wynn R, Burn T, Young PR. Ligand and coactivator recruitment preferences of peroxisome proliferator activated receptor alpha. J Steroid Biochem Mol Biol. 2002 Jul;81(3):217-25. doi: 10.1016/s0960-0760(02)00066-3
  10. Huber RM, Murphy K, Miao B, Link JR, Cunningham MR, Rupar MJ, Gunyuzlu PL, Haws TF, Kassam A, Powell F, Hollis GF, Young PR, Mukherjee R, Burn TC. Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters. Gene. 2002 May 15;290(1-2):35-43. doi: 10.1016/s0378-1119(02)00557-7
  11. Cheng D, Meegalla RL, He B, Cromley DA, Billheimer JT, Young PR. Human acyl-CoA:diacylglycerol acyltransferase is a tetrameric protein. Biochem J. 2001 Nov 1;359(Pt 3):707-14. doi: 10.1042/0264-6021:3590707
  12. Neville LF, Abdullah F, McDonnell PM, Young PR, Feuerstein GZ, Rabinovici R. Mob-1 expression in IL-2-induced ARDS: regulation by TNF-alpha. Am J Physiol. 1995 Dec;269(6 Pt 1):L884-90. doi: 10.1152/ajplung.1995.269.6.L884
  13. Wang X, Yue TL, Young PR, Barone FC, Feuerstein GZ. Expression of interleukin-6, c-fos, and zif268 mRNAs in rat ischemic cortex. J Cereb Blood Flow Metab. 1995 Jan;15(1):166-71. doi: 10.1038/jcbfm.1995.18
  14.  Liu T, Clark RK, McDonnell PC, Young PR, White RF, Barone FC, Feuerstein GZ. Tumor necrosis factor-alpha expression in ischemic neurons. Stroke. 1994 Jul;25(7):1481-8. doi:  10.1161/01.str.25.7.1481
  15. Liu T, McDonnell PC, Young PR, White RF, Siren AL, Hallenbeck JM, Barone FC, Feurestein GZ. Interleukin-1 beta mRNA expression in ischemic rat cortex. Stroke. 1993 Nov;24(11):1746-50; discussion 1750-1. doi: 10.1161/01.str.24.11.1746
  16. Liu T, Young PR, McDonnell PC, White RF, Barone FC, Feuerstein GZ. Cytokine-induced neutrophil chemoattractant mRNA expressed in cerebral ischemia. Neurosci Lett. 1993 Dec 24;164(1-2):125-8. doi: 10.1016/0304-3940(93)90873-j


Reviews


  1. Young, PR, Feuerstein, GZ. Cytokines in Endothelial Cell Survival and apoptosis: A role for protein kinases and caspases. In “Vascular Protection: Molecular Mechanisms, Novel Therapeutic Principles and Clinical Application”, Eds. Rubanyi, G.M., Dzau, V.Z. and Cooke, Publ. J.P.  Taylor and Francis, Malaysia, Singapore 2002. pp197-212. 
  2. Feuerstein GZ, Young PR. Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways. Cardiovasc Res. 2000 Feb;45(3):560-9. doi: 10.1016/s0008-6363(99)00372-7

Publications: Pulmonary

Peer Reviewed Literature


  1. Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R, et al. Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins. J Biol Chem. 1995 Apr 21;270(16):9459-71. doi: 10.1074/jbc.270.16.9459
  2. Morton TA, Bennett DB, Appelbaum ER, Cusimano DM, Johanson KO, Matico RE, Young PR, Doyle M, Chaiken IM. Analysis of the interaction between human interleukin-5 and the soluble domain of its receptor using a surface plasmon resonance biosensor. J Mol Recognit. 1994 Mar;7(1):47-55. doi: 10.1002/jmr.300070107
  3. Cafferkey R, McLaughlin MM, Young PR, Johnson RK, Livi GP. Yeast TOR (DRR) proteins: amino-acid sequence alignment and identification of structural motifs. Gene. 1994 Apr 8;141(1):133-6. doi: 10.1016/0378-1119(94)90141-4
  4. Cafferkey R, Young PR, McLaughlin MM, Bergsma DJ, Koltin Y, Sathe GM, Faucette L, Eng WK, Johnson RK, Livi GP. Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol Cell Biol. 1993 Oct;13(10):6012-23. doi: 10.1128/mcb.13.10.6012-6023.1993


Patent


  1. Browne, M.J., Young, P.R., Shatzman, A.R., Murphy, K.E., Chapman, C.G., Clinkenbeard, H.E.  Therapeutic Uses of Fusion Proteins between mutant IL 4/IL13 Antagonists and Immunoglobulins. U.S. Patent No. 5,783,181, July 1998.

Publications: Targets and Biomarkers

Peer Reviewed Literature


  1. Verma R, Su S, McCrann DJ, Green JM, Leu K, Young PR, Schatz PJ, Silva JC, Stokes MP, Wojchowski DM. RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development. J Exp Med. 2014 Aug 25;211(9):1715-22. doi: 10.1084/jem.20130624
  2. Zhu Y, Xu G, Patel A, McLaughlin MM, Silverman C, Knecht K, Sweitzer S, Li X, McDonnell P, Mirabile R, Zimmerman D, Boyce R, Tierney LA, Hu E, Livi GP, Wolf B, Abdel-Meguid SS, Rose GD, Aurora R, Hensley P, Briggs M, Young PR. Cloning, expression, and initial characterization of a novel cytokine-like gene family. Genomics. 2002 Aug;80(2):144-50. doi: 10.1006/geno.2002.6816
  3. Wang X, Xu L, Wang H, Young PR, Gaestel M, Feuerstein GZ. Mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 deficiency protects brain from ischemic injury in mice. J Biol Chem. 2002 Nov 15;277(46):43968-72. doi:  10.1074/jbc.M206837200
  4. Cheng D, Meegalla RL, He B, Cromley DA, Billheimer JT, Young PR. Human acyl-CoA:diacylglycerol acyltransferase is a tetrameric protein. Biochem J. 2001 Nov 1;359(Pt 3):707-14. doi: 10.1042/0264-6021:3590707
  5. Sims JE, Nicklin MJ, Bazan JF, Barton JL, Busfield SJ, Ford JE, Kastelein RA, Kumar S, Lin H, Mulero JJ, Pan J, Pan Y, Smith DE, Young PR. A new nomenclature for IL-1-family genes. Trends Immunol. 2001 Oct;22(10):536-7. DOI: 10.1016/s1471-4906(01)02040-3
  6. Kumar S, McDonnell PC, Lehr R, Tierney L, Tzimas MN, Griswold DE, Capper EA, Tal-Singer R, Wells GI, Doyle ML, Young PR. Identification and initial characterization of four novel members of the interleukin-1 family. J Biol Chem. 2000 Apr 7;275(14):10308-14. doi: 10.1074/jbc.275.14.10308
  7. Ozaki K, Kikly K, Michalovich D, Young PR, Leonard WJ. Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11439-44. doi: 10.1073/pnas.200360997
  8. Gum RJ, Young PR. Identification of two distinct regions of p38 MAPK required for substrate binding and phosphorylation. Biochem Biophys Res Commun. 1999 Dec 9;266(1):284-9. doi: 10.1006/bbrc.1999.1787
  9. Harrop JA, Reddy M, Dede K, Brigham-Burke M, Lyn S, Tan KB, Silverman C, Eichman C, DiPrinzio R, Spampanato J, Porter T, Holmes S, Young PR, Truneh A. Antibodies to TR2 (herpesvirus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines. J Immunol. 1998 Aug 15;161(4):1786-94. Doi: 10.4049/jimmunol.161.4.1786
  10. Gum RJ, McLaughlin MM, Kumar S, Wang Z, Bower MJ, Lee JC, Adams JL, Livi GP, Goldsmith EJ, Young PR. Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket. J Biol Chem. 1998 Jun 19;273(25):15605-10. doi: 10.1074/jbc.273.25.15605
  11. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem. 1998 Jun 5;273(23):14363-7. doi: 10.1074/jbc.273.23.14363
  12. Harrop JA, McDonnell PC, Brigham-Burke M, Lyn SD, Minton J, Tan KB, Dede K, Spampanato J, Silverman C, Hensley P, DiPrinzio R, Emery JG, Deen K, Eichman C, Chabot-Fletcher M, Truneh A, Young PR. Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth. J Biol Chem. 1998 Oct 16;273(42):27548-56. doi: 10.1074/jbc.273.42.27548
  13.  Tan KB, Harrop J, Reddy M, Young P, Terrett J, Emery J, Moore G, Truneh A. Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells. Gene. 1997 Dec 19;204(1-2):35-46. doi: 10.1016/s0378-1119(97)00509-x
  14. Young PR, McLaughlin MM, Kumar S, Kassis S, Doyle ML, McNulty D, Gallagher TF, Fisher S, McDonnell PC, Carr SA, Huddleston MJ, Seibel G, Porter TG, Livi GP, Adams JL, Lee JC. Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase bind in the ATP site. J Biol Chem. 1997 May 2;272(18):12116-21. doi: 10.1074/jbc.272.18.12116
  15.  Kwon BS, Tan KB, Ni J, Oh KO, Lee ZH, Kim KK, Kim YJ, Wang S, Gentz R, Yu GL, Harrop J, Lyn SD, Silverman C, Porter TG, Truneh A, Young PR. A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation. J Biol Chem. 1997 May 30;272(22):14272-6. doi: 10.1074/jbc.272.22.14272
  16. Kumar S, McDonnell PC, Gum RJ, Hand AT, Lee JC, Young PR. Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. Biochem Biophys Res Commun. 1997 Jun 27;235(3):533-8. doi: 10.1006/bbrc.1997.6849
  17. Einstein R, Jackson JR, D'Alessio K, Lillquist JS, Sathe G, Porter T, Young PR. Type I IL-1 receptor: ligand specific confirmation differences and the role of glycosylation in ligand binding. Cytokine. 1996 Mar;8(3):206-13. doi: 10.1006/cyto.1996.0029
  18.  Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R, et al. Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins. J Biol Chem. 1995 Apr 21;270(16):9459-71. doi: 10.1074/jbc.270.16.9459
  19. Clifton AD, Young PR, Cohen P. A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress. FEBS Lett. 1996 Sep 2;392(3):209-14. doi: 0.1016/0014-5793(96)00816-2
  20. McLaughlin MM, Kumar S, McDonnell PC, Van Horn S, Lee JC, Livi GP, Young PR. Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase. J Biol Chem. 1996 Apr 5;271(14):8488-92. doi: 10.1074/jbc.271.14.8488
  21. Doherty MJ, Young PR, Cohen PT. Amino acid sequence of a novel protein phosphatase 1 binding protein (R5) which is related to the liver- and muscle-specific glycogen binding subunits of protein phosphatase 1. FEBS Lett. 1996 Dec 16;399(3):339-43. doi: 10.1016/s0014-5793(96)01357-9
  22.  Kumar S, McLaughlin MM, McDonnell PC, Lee JC, Livi GP, Young PR. Human mitogen-activated protein kinase CSBP1, but not CSBP2, complements a hog1 deletion in yeast. J Biol Chem. 1995 Dec 8;270(49):29043-6. doi: 10.1074/jbc.270.49.29043
  23. Bennett D, Morton T, Breen A, Hertzberg R, Cusimano D, Appelbaum E, McDonnell P, Young P, Matico R, Chaiken I. Kinetic characterization of the interaction of biotinylated human interleukin 5 with an Fc chimera of its receptor alpha subunit and development of an ELISA screening assay using real-time interaction biosensor analysis. J Mol Recognit. 1995 Jan-Apr;8(1-2):52-8. doi: 10.1002/jmr.300080109
  24.  Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R, et al. Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins. J Biol Chem. 1995 Apr 21;270(16):9459-71. doi: 10.1074/jbc.270.16.9459
  25. Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR, Lee JC. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett. 1995 May 8;364(2):229-33. doi: 10.1016/0014-5793(95)00357-f
  26. McDonnell PC, DiLella AG, Lee JC, Young PR. Localization of the human stress responsive MAP kinase-like CSAIDs binding protein (CSBP) gene to chromosome 6q21.3/21.2. Genomics. 1995 Sep 1;29(1):301-2. doi: 10.1006/geno.1995.1252
  27.  Ben-Baruch A, Xu L, Young PR, Bengali K, Oppenheim JJ, Wang JM. Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors. C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3. J Biol Chem. 1995 Sep 22;270(38):22123-8. doi: 10.1074/jbc.270.38.22123
  28. Symons JA, Young PR, Duff GW. Soluble type II interleukin 1 (IL-1) receptor binds and blocks processing of IL-1 beta precursor and loses affinity for IL-1 receptor antagonist. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1714-8. doi: 10.1073/pnas.92.5.1714
  29. Burrows SD, Doyle ML, Murphy KP, Franklin SG, White JR, Brooks I, McNulty DE, Scott MO, Knutson JR, Porter D, Young PR. and Hensley P.  Determination of the monomer-dimer equilibrium of interleukin-8 reveals it is a monomer at physiological concentrations. Biochemistry. 1994 Nov 1;33(43):12741-5. doi: 10.1021/bi00209a002
  30.  Morton TA, Bennett DB, Appelbaum ER, Cusimano DM, Johanson KO, Matico RE, Young PR, Doyle M, Chaiken IM. Analysis of the interaction between human interleukin-5 and the soluble domain of its receptor using a surface plasmon resonance biosensor. J Mol Recognit. 1994 Mar;7(1):47-55. doi: 0.1002/jmr.300070107
  31. Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, Strickler JE, McLaughlin MM, Siemens IR, Fisher SM, Livi GP, White JR, Adams JL, Young PR. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994 Dec 22-29;372(6508):739-46. doi: 10.1038/372739a0
  32. Eng WK, Faucette L, McLaughlin MM, Cafferkey R, Koltin Y, Morris RA, Young PR, Johnson RK, Livi GP. The yeast FKS1 gene encodes a novel membrane protein, mutations in which confer FK506 and cyclosporin A hypersensitivity and calcineurin-dependent growth. Gene. 1994 Dec 30;151(1-2):61-71. doi: 10.1016/0378-1119(94)90633-5
  33. Cafferkey R, McLaughlin MM, Young PR, Johnson RK, Livi GP. Yeast TOR (DRR) proteins: amino-acid sequence alignment and identification of structural motifs. Gene. 1994 Apr 8;141(1):133-6. doi: 10.1016/0378-1119(94)90141-4
  34.  Simon PL, Kumar V, Lillquist JS, Bhatnagar P, Einstein R, Lee J, Porter T, Green D, Sathe G, Young PR. Mapping of neutralizing epitopes and the receptor binding site of human interleukin 1 beta. J Biol Chem. 1993 May 5;268(13):9771-9. doi: 10.1016/S0021-9258(18)98414-0
  35. Camacho NP, Smith DR, Goldman A, Schneider B, Green D, Young PR, Berman HM. Structure of an interleukin-1 beta mutant with reduced bioactivity shows multiple subtle changes in conformation that affect protein-protein recognition. Biochemistry. 1993 Aug 31;32(34):8749-57. doi: 10.1021/bi00085a005
  36. Cafferkey R, Young PR, McLaughlin MM, Bergsma DJ, Koltin Y, Sathe GM, Faucette L, Eng WK, Johnson RK, Livi GP. Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol Cell Biol. 1993 Oct;13(10):6012-23. doi: 10.1128/mcb.13.10.6012-6023.1993
  37.  Krasney PA, Young PR. Further aspects of IL-1 beta secretion revealed by transfected monkey kidney cells. Cytokine. 1992 Mar;4(2):134-43. doi: 10.1016/1043-4666(92)90048-v
  38.  Hazuda DJ, Strickler J, Simon P, Young PR. Structure-function mapping of interleukin 1 precursors. Cleavage leads to a conformational change in the mature protein. J Biol Chem. 1991 Apr 15;266(11):7081-6. Doi: 10.1016/S0021-9258(20)89612-4
  39. Hassell AM, Johanson KO, Goodhart P, Young PR, Holskin BP, Carr SA, Roberts GD, Simon PL, Chen MJ, Lewis M. Preliminary X-ray crystallography studies of recombinant human interleukin-1 alpha. Purification and structural characterization. J Biol Chem. 1989 Mar 25;264(9):4948-52. Doi:  10.1016/S0021-9258(18)83682-1 
  40. Young PR, Sylvester D. Cloning of rabbit interleukin-1 beta: differential evolution of IL-1 alpha and IL-1 beta proteins. Protein Eng. 1989 May;2(7):545-51. Doi: 10.1093/protein/2.7.545
  41. Smith MF Jr, Kueppers FR, Young PR, Lee JC. A rapid and quantitative method for the determination of interleukin-1 alpha and -beta mRNA expression in human monocytes and macrophages. J Immunol Methods. 1989 Mar 31;118(2):265-72. doi: 10.1016/0022-1759(89)90015-x
  42.  Lee JC, Simon PL, Young PR. Constitutive and PMA-induced interleukin-1 production by the human astrocytoma cell line T24. Cell Immunol. 1989 Feb;118(2):298-311. doi: 10.1016/0008-8749(89)90379-1
  43.  Hazuda D, Webb RL, Simon P, Young P. Purification and characterization of human recombinant precursor interleukin 1 beta. J Biol Chem. 1989 Jan 25;264(3):1689-93. Doi: 10.1016/S0021-9258(18)94241-9
  44.  Lichenstein H, Brawner ME, Miles LM, Meyers CA, Young PR, Simon PL, Eckhardt T. Secretion of interleukin-1 beta and Escherichia coli galactokinase by Streptomyces lividans. J Bacteriol. 1988 Sep;170(9):3924-9. doi: 10.1128/jb.170.9.3924-3929.1988. doi: 10.1128/jb.170.9.3924-3929.1988
  45.  Lillquist JS, Simon PL, Summers M, Jonak Z, Young PR. Structure-activity studies of human IL-1 beta with mature and truncated proteins expressed in Escherichia coli. J Immunol. 1988 Sep 15;141(6):1975-81. Doi: 10.4049/jimmunol.141.6.1975
  46.  Hazuda DJ, Lee JC, Young PR. The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin 1 alpha and interleukin 1 beta. J Biol Chem. 1988 Jun 15;263(17):8473-9. Doi: 10.1016/S0021-9258(18)68502-3
  47. Young PR, Hazuda DJ, Simon PL. Human interleukin 1 beta is not secreted from hamster fibroblasts when expressed constitutively from a transfected cDNA. J Cell Biol. 1988 Aug;107(2):447-56. doi: 10.1083/jcb.107.2.447
  48. Meyers CA, Johanson KO, Miles LM, McDevitt PJ, Simon PL, Webb RL, Chen MJ, Holskin BP, Lillquist JS, Young PR. Purification and characterization of human recombinant interleukin-1 beta. J Biol Chem. 1987 Aug 15;262(23):11176-81. Doi: 10.1016/S0021-9258(18)60941-X
  49.  Young PR, Kallenbach NR. Site exclusion and sequence specificity in binding of 9-aminoacridine to the deoxytetranucleotide dpApGpCpT. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6453-7. doi: https://www.pnas.org/doi/10.1073/pnas.77.11.6453.


Reviews


  1.  Young PR. Perspective on the discovery and scientific impact of p38 MAP kinase. J Biomol Screen. 2013 Dec;18(10):1156-63. doi: 10.1177/1087057113497401
  2. Young PR. Pharmacological modulation of cytokine action and production through signaling pathways. Cytokine Growth Factor Rev. 1998 Sep-Dec;9(3-4):239-57. doi: 10.1016/s1359-6101(98)00011-2. 
  3. Lee JC, Young PR. Role of CSB/p38/RK stress response kinase in LPS and cytokine signaling mechanisms. J Leukoc Biol. 1996 Feb;59(2):152-7. doi: 10.1002/jlb.59.2.152.
  4. Young PR. Protein hormones and their receptors. Curr Opin Biotechnol. 1992 Aug;3(4):408-21. doi: 10.1016/0958-1669(92)90170-n.
  5. Berman HM, Young PR. The interaction of intercalating drugs with nucleic acids. Annu Rev Biophys Bioeng. 1981;10:87-114. doi: 10.1146/annurev.bb.10.060181.000511.


Patents


  1. Deen, K.C., Hurle, M.R., Young, P.R., Tan, K.B. "Tumor necrosis related receptor, TR7". US Patent No. 7,049,422, May 2006.
  2. Erickson-Miller, C.L., Holmes, S.D., Taylor, A.H., Young, P.R. “Erythropoietin Receptor Antibodies”. U.S. Patent No. 6,998,124, Feb. 2006.
  3. Deen, K.C., Hurle, M.R., Young, P.R., Tan, K.B. "Tumor necrosis related receptor, TR7". US Patent No. 6,660,839, Dec. 2003.
  4. Young P.R., Tan, K.B., Truneh, A., Lyn, S.D.P. “Method to identify substances which stimulate or inhibit the binding of TL2 (TRAIL) to TR5”. European Patent No. EP0867509 B1, Aug.  2002.
  5. Young, P.R. “Interleukin-1 receptor antagonist beta (IL-1rabeta)”. US Patent No. 6,399,573, June 2002.
  6. Emery, J, Tan, K.B., Truneh, A, Young, P.R. “Tumor necrosis related receptor, TR4”. European Patent No. EP0861850 B1, May 2002.
  7. Lee, J.C., Adams, J.L., Gallagher, T.F., Green, D.W., Heys, J.R., McDonnell, P.C., McNulty, D.E., Young, P.R., Strickler, J.E. “Antibodies produced against cytokine suppressive anti-inflammatory drug binding protein”. US Patent No. 6,361,773, Mar. 2002.
  8. Brigham-Burke, M.R., Young, P.R. “Method of identifying agonist and antagonists for tumor necrosis factor related receptors TR1 and TR2”. US Patent No. 6,346,388, Feb. 2002.
  9. McDonnell, P.C. and Young, P.R. “Interleukin-1 homologue, IL-1H4”. US Patent No. 6,342,371, Jan. 2002.
  10. Deen, K.C., Young, P.R., Marshall, L.A., Roshak, A.K., Tan, K.B., Truneh, A. “Tumor Necrosis Factor Related Receptor, TR6”. US Patent No. 6,313,269, Nov. 2001.
  11. Young, P.R., Cohen, P.T.W. and Cohen, P. “Protein Phosphatase 1 Binding Protein, R5”. US Patent No. 6,297,359, Oct 2, 2001.
  12. McDonnell, P.C., Young, P.R. and Zou, J. “A method of identifying agonists and antagonists for tumor necrosis factor receptor TR1”. US Patent No. 6,297,022, Oct. 2001.
  13. Abdel-Meguid, S.S., Aurora, R., Bergsma, D., Ellis, C.E., Guerrera, S.E., Hensley, P., Mooney, J.L., Rose, G.D., Young, P.R., Zhu, Y. “Cytokine family member EF-7”. US Patent No. 6,245,550, June 2001.
  14. Young, P.R. “Interleukin-1 receptor antagonist beta (IL-1RAb)”. US Patent No. 6,054,559, Apr. 2000.
  15. McDonnell, P.C. and Young, P.R. “Drug binding protein.” US Patent No. 6,033,873, Mar. 2000.
  16. Deen K., Hurle, M., Young, P.R. and Tan, K.B. "DNA encoding tumor necrosis related receptor, TR7". US Patent No. 6,013,476, Jan. 2000.
  17. Lee, J.C., Adams, J.L., Gallagher, T.F., Green, D.W., Heys, R.R., McDonnell, P.C. McNulty, D.E., Strickler, J.E., Young, P.R. “Polynucleotides encoding cytokine suppressive anti-inflammatory drug binding proteins”. U.S. Patent No. 5,955,366, Sept.1999.
  18. Young, P.R., James, I. and Connor, J. "DNA encoding members of the IL-1 family, IL-1 delta”. U.S. Patent No. 5,945,310, Aug. 1999.
  19. Cohen, P.T.W., Cohen, P. and Young, P.R. "A protein phosphatase 1 binding protein R5". U.S. Patent No. 5,939,284, Aug. 1999.
  20. 20.  Hurle, M., McDonnell, P.C., McNulty, D., Siemens, I., Young, P.R. and Yue, T-L. "Smooth Muscle Cell-Derived Migration Factor". U.S. Patent No. 5,916,758, June 1999.
  21. Emery, J.G., Tan, K.B., Truneh, A., Young, P.R. "DNA encoding Tumor Necrosis Factor Related Receptor, TR4". U.S. Patent No. 5,885,800, Mar.1999.
  22. McDonnell, P.C., Young, P.R. "Drug Binding protein". U.S. Patent No. 5,869,043, Feb. 1999.
  23.  Young, P.R.  "DNA encoding Interleukin-1 Receptor Antagonist Beta (IL-1RAb)". U.S Patent No. 5,863,769, Jan. 1999.
  24. Lee, J.C., Adams, J.L., Gallagher, T.F., Green, D.W., Heys, R.R., McDonnell, P.C. McNulty, D.E., Strickler, J.E., Young, P.R. Cytokine Suppressive Anti-Inflammatory Drug Binding Protein. U.S. Patent No. 5,783,664, July 1998.
  25. Browne, M.J., Young, P.R., Shatzman, A.R., Murphy, K.E., Chapman, C.G., Clinkenbeard, H.E.  Therapeutic Uses of Fusion Proteins between mutant IL 4/IL13 Antagonists and Immunoglobulins. U.S. Patent No. 5,783,181, July 1998.
  26.  Lee, J.C., Adams, J.L., Gallagher, T.F., Green, D.W., Heys, R.R., McDonnell, P.C. McNulty, D.E., Strickler, J.E., Young, P.R. Cytokine Suppressive Anti-Inflammatory Drug Binding Protein. U.S. Patent No. 5,777,097, July 1998

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