Constantinos G. Panousis, Ph.D.

*** ******** ***** ****

Penn Hills, Pittsburgh, PA 15235

Mobile: 201-***-****

Email: acfyz4@r.postjobfree.com

Summary:

Senior Principal Scientist with expertise in Molecular Biology and

Pharmacology. Area of interest; Infectious Diseases, Atherosclerosis,

Diabetes, and Kidney diseases

.

. Development of new qPCR based diagnostic assay for HIV drug resistance.

. Successfully delivered clinical drug candidates for an HDL raising

program that entered Phase I clinical studies (RG7273).

. Project Leader for drug discovery programs with more than 20 team members

including Chemistry, ADME and Toxicology.

. Programs for both small molecule and biologic drug development.

. Strong expertise in molecular biology, cell-based and in vitro assay

development, receptor pharmacology, enzymology.

. Experienced on establishing and developing new animal models for

metabolic diseases.

. Evaluating in house new target proposals, in-licensing opportunities, and

participated in due diligence for programs and company acquisitions.

Professional Experience:

University of Pittsburgh, Translational Research, Pittsburgh, PA, USA

Med-Div of Infectious Diseases

Research Project Manager (2012-2014)

. HIV Research, analyzing samples from clinical studies for HIV drug

resistance, using sequencing.

. Developed a new diagnostic assay that can detect reliably drug resistance

to HIV ARV therapies; work awarded by grant from Innovation Works.

. Detection of drug resistant minority species in patient samples from

clinical studies using anti-retroviral HIV therapies.

University of Pittsburgh, Drug Discovery, Pittsburgh, PA, USA

Drug Discovery Institute

Consultant (2012-2012)

. Validation of 14 projects in Infectious Diseases, Oncology, Metabolic

Diseases.

. Established criteria in relation to true developmental stage,

drugability, competition, and out licensing opportunities for current and

future project prioritization interacting directly with the Head of the

Drug Discovery Institute.

F. Hoffmann-La Roche, Pharmaceutical Research, Nutley, NJ, USA

Metabolic and Vascular Diseases

Senior Principal Scientist (2008-2011)

. Target Advocate for two anti-inflammatory projects for the treatment of

Acute Kidney Injury using an anti-cytokine antibody approach and

developing small molecular weight inhibitors for an intracellular

protease.

. Validation of a new GPCR targeting the adipose tissue as a new target for

atherosclerosis and diabetes and identification of a potent lead series.

. Led and coordinate efforts with teams from the in vivo group, discovery

technologies, chemistry, and non-clinical safety.

. Established in vitro assays for biomarker characterization in urine and

plasma for kidney functionality and assisted on the development in house

of an Acute Kidney Injury mouse model.

. Established biochemical assays to assess pharmacology of Incretin

receptors and their effects on adipose tissue.

. Present regularly project reviews and proposals to the local management

and to the global therapeutic leadership team.

. Organized a GPCR journal club.

. Managed a MD/Ph.D. and a MS scientist.

F. Hoffmann-La Roche, Pharmaceutical Research, Basel, Switzerland

Metabolic and Vascular Diseases

Senior Principal Scientist (2000-2008)

. Identified the mode of action for a series of HDL-raising compounds as

ABCA1-inducers driving project to clinical lead series selection and

entering Phase-I trials (RG7273).

. Project leader for a dyslipidemia program in collaboration with the ETH

in Zurich targeting a recombinant apolipoprotein approach for HDL

raising, leading a group of protein chemists, and in vivo scientists.

. Validated an in licensing opportunity for a new form of

biopharmaceuticals, and diagnostic reagents, by developing assays for

measuring apolipoproteins and compared them with existing tests.

. Initiated a program on the identification of biomarkers for HDL

functionality in collaboration with the proteomics group.

. Proposed, initiated and led the biochemistry/pharmacology effort on the

NiacinR (GPR109A) target, resulted in five patent publications.

. Established all biochemical assays for HM74A to assess receptor

pharmacology, secondary assays to determine anti-lipolytic activity in

adipocytes and macrophages for derisking.

. Using Affymetrix chip arrays analyze differential expression on

macrophages from Tangier patients compared to controls in collaboration

with the university of Muenster.

. Established the CETPxApoB Tg mice as a rodent model to determine the HDL

raising effects of Niacin.

. Using mutagenesis analysis characterized the binding pocket of HM74A

(GPR109A) aiding on the identification of new compound series and

establishing SAR.

. Led a program on the transcriptional upregulation of ABCA1 as a mode to

raise HDL.

. Validated targets derived from an Y2H screen through an external

collaboration using mutagenesis and functional analysis.

. Established a high throughput cholesterol efflux assay that used

extensively in various programs to identify new HDL raising agents.

. Characterized the HDL functionality of clinical samples derived from the

phase I/II trials of dalcetrapib (CETP inhibitor), currently under phase

III trials.

. Participated in in-licensing opportunities within the dyslipidemia group,

and provided evaluation reports to management.

. Organized journal clubs focusing on potential new metabolic drug targets.

. Managed three associates, two MS and one BS scientist, and had four

students.

Training:

Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN

Division of Cardiovascular Research

Post-Doctoral Scientist (1997-2000)

Post Doctoral training in dyslipidemia in the Laboratory of Dr. Steven

Zuckerman, working on cholesterol metabolism in macrophage foam cells, the

hallmark of atherosclerosis. From this work by using microarrays, I

identify a strong relation between inflammatory responses and cholesterol

metabolism that were mediated mainly by the down-regulation of the

cholesterol efflux transporter ABCA1, proving that certain inflammatory

responses directly linked with the cholesterol accumulation in macrophages.

Education:

University of Pittsburgh, Pittsburgh, PA

Infectious Diseases and Microbiology

Ph.D. in Molecular Biology/Virology (1997)

Ph.D. Thesis under the supervision of Dr. David Rowe, studying the Latent

Membrane Protein 2A (LMP2A) of Epstein Barr Virus (EBV). This work was

focused on signal transduction and resulted in the identification of the

ITAM motifs similar to B and T cell receptor within the LMP2A and its

association with MAPK linking the activation of virus to the proliferation

status of B cells.

University of Athens, Athens, Greece

Department of Chemistry

B.Sc. in Chemistry (1988)

Electives: Biochemistry and Food Chemistry.

Professional Development:

Mini-MBA course: Program on Biopharma Innovation, Center for Management

Development Rutgers University, New Jersey, USA.

International Institute for Management Development (IMD), Lausanne,

Switzerland

" Leadership & Teamwork Course"

LTK1: Introductory course in Laboratory Animal Science, Basel, Switzerland

LTK2: Training for persons responsible for directing Animal Experiments,

Zurich, Switzerland

Teaching Experience:

Graduate School: Infectious Diseases and Microbiology

* Teaching Assistant in Immunology for graduate students in the School of

Public Health at the University of Pittsburgh

* Lecturer for Signal Transduction to graduate students at the department

of Infectious Diseases and Microbiology, at the University of Pittsburgh.

Awards:

Grant Award from the Commonwealth of Pennsylvania through Innovation

Works (2014): "Sensitive and Affordable Test for the Detection of HIV

Drug Resistance"

Roche Pharma CEO Award (2009):

"Innovative modulator of the elusive ABCA1 cholesterol efflux pathway".

Best Dissertation Award: Graduate school of Public Health, University of

Pittsburgh (1998).

The Omicron Chapter of Delta Omega the National Honor Society in Public

Health Award

Personal Data:

Permanent Resident of United States.

Publications and Patents:

Constantinos G. Panousis, Elias K. Halvas, John W. Mellors. 2014. SENSITIVE

ALLELE SPECIFIC PCR ASSAY FOR THE DETECTION OF HIV-1 MINOR VARIANTS AND

LINKED DRUG RESISTANCE MUTATIONS

J. Clin. Microb. (in preparation)

Jane Hitti, Elias K. Halvas, Constantinos G. Panousis, Lu Zheng, Joseph

Kabanda, Frank Taulo, Nagalingeswaran Kumarasamy, Jean William Pape, Umesh

Lalloo, Heather Sprenger, Karin L. Klingman, Ellen S. Chan, Deborah

McMahon, John W. Mellors. 2014EFFECT OF SHORT COURSE MATERNAL

ANTIRETROVIRAL REGIMENS AFTER SINGLE-DOSE NEVIRAPINE ON HIV-1 TRANSMISSION

AND DRUG RESISTANCE IN INFANTS: ACTG A5207

JAIDS (Submitted)

Constantinos G. Panousis, Elias K. Halvas, John W. Mellors. Allele Specific

PCR Assay for the Detection of DNA Mutations. US61/892993, 2013.

Kratochwil N., Gatti-McArthur S., Hoener M.C., Lindemann L., Christ A.D.,

Green L.G., Guba W., Martin R.E., Malherbe P., Porter R.H., Slack J.P.,

Winning M., Dehmlow H., Grether U., Hertel C., Narquizian R., Panousis

C.G., Loczewski S., Steward L. G-protein-Coupled Receptor (GPCR)

Transmembrane Binding Pockets and their Applications in GPCR Research and

Drug Discovery A survey: Current Topics in Medicinal Chemistry 2011 Aug;11

(15) 1902-24

Peters J.U., Kuhne H., Dehmlow H., Grether U., Conte A., Hainzl D., Hertel

C., Kratochwil N.A., Otteneder M., Narquizian R., Panousis C.G., Ricklin

F., Rover S. Pyrido pyrimidinones as selective agonists of the high

affinity niacin receptor GPR109A: optimization of in vitro activity. Bioorg

Med Chem Lett. 2010 Sep15;20(18):5426-30.

Hebeisen Paul, Panousis C.G., Roever Stephan. 3-Trifluoromethyl-pyrazine-2-

carboxylic acid amide derivatives as HDL-cholesterol raising agents.

WO2009/121741 A1, Oct. 08, 2009.

Andjelkovic M., Benardeau A., Chaput E., Hebeisen P., Nettekoven M., Obst

Sander U., Panousis C.G., Roever S. 3-pyridinecarboxamide and 2-

pyrazinecarboxamide derivatives as HDL-cholesterol raising agents.

WO2008/040651 A1, April 10, 2008.

Conte A., Dehmlow H., Grether U., Kratochwil N.A., Kuehne H., Narquizian

R., Panousis C.G., Peters JU, Ricklin F. Preparation of novel aza-

pyridopyrimidinone as G-protein coupled receptor (HM74A) agonists

US20080234277 A1, 2008.

Conte A., Dehmlow H., Grether U., Kratochwil N.A., Kuehne H., Narquizian

R., Panousis C.G., Peters JU, Ricklin F, Roever S. Preparation of novel aza-

pyridopyrimidinone as G-protein coupled receptor (HM74A) agonists

WO2007/134986 A1, 2007.

Dehmlow H, Grether U, Kratochwil N, Narquizian R, Panousis C.G..

Preparation of acylaminothiophenecarboxylates as HM74A agonists.

US20070161650 A1, 2007.

Dehmlow H, Grether U, Kratochwil N, Narquizian R, Panousis C.G..

Preparation of acylaminothiophenecarboxylates as HM74A agonists.

US20070072873 A1, 2007.

Dehmlow H, Grether U, Kratochwil N, Narquizian R, Panousis C.G., PetersJ.U.

Preparation of benzoylanthranililc acid derivatives as G protein-coupled

receptor HM74A agonists. US20060281810 A1, 2006.

Wang XQ, Panousis C.G., Alfaro ML, Evans GF, Zuckerman SH. Interferon-gamma-

mediated down-regulation of cholesterol efflux and ABCA1 expression is by

the Stat1 pathway.

Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):e5-9.

Panousis, C.G., and Zuckerman S.H. TGF-beta increases cholesterol efflux

and ABCA1 expression in macrophage-derived foam cells: opposing the effects

of IFN-gamma.

J Lipid Res. 2001 May;42(5):856-63.

Zuckerman S.H., Panousis, C.G., Evans G.F.,. TGF-beta reduced binding of

high-density lipoproteins in murine macrophages and macrophage-derived foam

cells.

Atherosclerosis. 2001 Mar;155(1):79-85.)

Zuckerman, S.H., Panousis, C.G., Mizrahi J., and Evans G.F.. The effect of

gamma-interferon to inhibit macrophage-high density lipoprotein

interactions is reversed by 15-deoxy-delta12,14-prostaglandin J2.

Lipids. 2000 Nov;35(11):1239-47.

Panousis, C.G., and Zuckerman, S.H. 2000. Interferon gamma induces down

regulation of the expression of the Tangier's disease gene (ABCA1) in

macrophage derived foam cells. Arteriosclerosis Thrombosis and Vascular

Biology, 20:1565-1571. (Editorial Review - Tall, A & Schindler C. -

Arteriosclerosis Thrombosis and Vascular Biology 20:1423-1424).

Panousis, C.G., and Zuckerman, S.H. 2000. Regulation of cholesterol

distribution in macrophage derived foam cells by gamma interferon (IFN

Journal of Lipid Research 41:75-83.

Panousis, C.G., and Rowe, T.D.1997. The Epstein-Barr Virus Latent Membrane

Protein 2 associates with and is a substrate for Mitogen Activated Protein

Kinase. Journal of Virology 71(6):4752-4760.

Presentations:

Panousis, C.G., and Zuckerman S.H. 2000. Interferon gamma (IFN-?) induces

the down regulation of the Tangier's disease gene (ABCA1) in macrophage-

derived foam cells. First Conference on Arteriosclerosis, Thrombosis, and

Vascular Biology, Denver, CO.

Panousis, C.G., and Zuckerman S.H. 1999. Regulation of cholesterol

trafficking in macrophage derived foam cells by gamma interferon.7th

International Cytokine Conference, Hilton Head, SC.

Panousis, C. G., and Rowe, D.T. 1997. The Epstein-Barr Virus Latent

Membrane Protein 2 associates with and is a substrate for Mitogen Activated

Protein Kinase. XXII International Hepresvirus Workshop, San Diego, CA.

Panousis, C.G., and David T. Rowe.1993. EBV Terminal Protein 1 (TP1)

Carries the Multichain Immune Recognition Receptor (MIRR / ITAM)

Cytoplasmic Motif. XVIII International Herpesvirus Workshop, Pittsburgh,PA

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