Eric G. Marcusson, Ph.D.

San Francisco, CA

Summary of Qualifications

 

I am a scientific director with more than 20 years of experience in biotechnology industry. Throughout my career I have worked with innovative technologies to identify genes that make effective targets for specific molecularly-targeted therapies and helped to drive these therapies into the clinic. Recently, I have championed the use of genomic and molecular characterization to better match animal models with the right patient populations to increase the effectiveness of molecularly targeted therapies. I have played a major role in starting a new company and have a passion for evaluating novel technologies that may lead to more efficient drug discovery platforms.

 

Highlights

 

  • At Ionis Pharmaceuticals, led the preclinical research team responsible for building data packages to move two oncology compounds into the clinic and kill two other programs before candidate nomination in collaboration with Eli Lilly
  • Coauthor of an SBIR grant on siRNA therapeutics that was funded for phase 1 and 2
  • Was part of a small group that founded a company, Regulus Therapeutics, that had a successful initial public offering and will bring novel drugs to the clinic in the next year
  • Involved in business development activities that led to the signing of multiple alliances and interacted with investment companies to help set up the base for a successful IPO
  • Led collaborations with large pharmaceutical companies, medical centers and individual academic groups for discovery and development of oncology drugs
  • Received promotions at every company worked at during career
  • Successfully founded a consulting company with many clients in the drug discovery or venture capital areas

 

 

Professional Experience

 

2013-Present              Marcusson Consulting, San Francisco, CA

                                         Founder

  • Providing expert advice based on 20+ years of experience in early preclinical drug development using RNA therapeutics in the areas of oncology and metabolic diseases
  • Helping investigators to better understand the complex biology surrounding microRNAs and other noncoding RNA
  • Evaluating oncology and RNA therapeutic companies as investment opportunities for venture capitalists and other financial institutions

 

2007-2013                         Regulus Therapeutics, San Diego, CA

2011-2013                            Senior Director, Oncology and Basic Mechanisms

2007-2010                          Director, Oncology

 

  • Investigated the therapeutic potential of modulating microRNA activity in oncology
  • Was part of the scientific side of a team that signed alliances with three large pharmaceutical companies and helped define drug targets and discovery plans for the projects
  • Led a large collaboration with Samsung Medical Center to identify targeted drug candidates in glioblastoma multiforme which are now in preclinical development
  • Characterized the effectiveness of several lipid nanoparticle systems to deliver microRNA mimics to the liver and liver tumors for therapeutic purposes
  • Worked on identifying subpopulations of cancer patients that would be most likely to respond to specific targeted therapy through the use of molecular characterization on multiple levels
  • Linked animal models to specific subpopulations of cancer patients to more efficiently determine the therapeutic potential of targeted therapies
  • Collaborated with large pharmaceutical partners on preclinical packages of three cancer targets in multiple cancer types
  • Coordinated with the Chemistry, ADME and Bioinformatics groups to identify the optimal compounds for our clinical programs
  • Designed and performed experiments to help better understand the mechanisms by which microRNAs exert their effects on gene expression and better characterize the mechanism of action of Regulus’ drugs

 

2000-2007                         Isis Pharmaceuticals, Carlsbad, CA

2004-2007                           Director

2003-2004                          Associate Director

2001-2002                           Assistant Director

2000-2001                           Senior Scientist

 

  • Led drug discovery programs in the areas of oncology and metabolic diseases
  • Supervised the Isis preclinical research team that placed two drugs into clinical trials for oncology in collaboration with Eli Lilly
  • Designed program to identify best potential drug target in hepatocellular carcinoma
  • Managed multiple collaborations with academic groups and pharmaceutical companies
  • Supervised a group of 10 scientists generating data through human cell-based phenotypic assays in the areas of oncology, immunology, metabolic diseases and angiogenesis

 

1998-2000                     Immusol, Inc.

1999-2000                      Scientist II

1998-1999                        Scientist

 

  • Constructed a viral-based randomized ribozyme library for use in functional genomics screens
  • Used the viral library to identify new tumor suppressor genes and potential therapeutic targets for oncology
  • Identified genes that regulate the translation of the HCV transcript through an IRES-mediated mechanism

 

 

Education:

 

University of California, San Diego, School of Medicine, Awarded Ph.D. in Biomedical Sciences

 

University of California, San Diego, Graduated Magna Cum Laude with a B.A. in Cell Biology and Physiological Psychology

 

 

 

Selected Patents and Public Patent Applications (of more than 50)

 

Antisense modulation of novel anti-apoptotic Bcl-2-related proteins (USP 6,001,992)

Antisense inhibition of Fas mediated signaling (as amended) (USP 6,204,055)

Antisense modulation of extracellular-signal-regulated kinase-6 expression (PCT/US03/16214)

Modulation of HIF1alpha and HIF2alpha expression (USP 7,217,572)

Modulation of HIF1-beta expression (USP 7,799,764)

Oligomeric compounds and compositions for use in modulation of small non-coding RNAs (US2009-0317907)

Modulation of eIF4E expression (USP 7,425,544)

Identification of novel pathways, genes and promoter motifs regulating adipogenesis (USP 7,759,318)

Targeting microRNAs for the treatment of liver cancer (US2010-0267814)

Double strand compositions comprising differentially modified strands for use in gene modulation (US2011-0046206)

MicroRNA Compositions and Methods (WO 2011088309)

 

 

Invited Presentations

 

January, 2013            Keystone Symposium on Noncoding RNA in Development and Cancer, Vancouver, BC, Canada

January 2012             AACR Special Conference on Noncoding RNAs and Cancer, Miami, FL

April, 2012                 Experimental Biology, San Diego, CA

April, 2012                 Research in Progress Talk at UCSF Hematology/Oncology Grand Rounds, San Francisco, CA

June, 2011                  BIO International Convention, Washington, DC

March, 2011                CHI’s Seventh Annual microRNAs in Disease and Development, Cambridge, MA

February, 2011          Keystone Symposium on RNA and Cancer, Banff, AB, Canada

October, 2010            Annual Meeting of the Oligonucleotide Therapeutics Society, Dana Point, CA

March, 2010               Keystone Symposium on Novel Cancer Therapeutics, Victoria, BC, Canada

September, 2009       5th Modern Drug Discovery and Development Summit, San Diego, CA

June 2009                   Keystone Symposium on microRNAs and Cancer, Keystone, CO

August, 2008             Joint Metastasis Research Society-AACR Conference on Metastasis, Vancouver, BC, Canada

May, 2006                  TIDES Conference, La Costa, CA

 

 

Publications

Yaghi NK, Wei J, Hashimoto Y, Kong LY, Gabrusiewicz K, Nduom EK, Ling X, Huang N, Zhou S, Kerrigan BC, Levine JM, Fajt VR, Levine G, Porter BF, Marcusson EG, Tachikawa K, Chivukula P, Webb DC, Payne JE, Heimberger AB. Immune modulatory nanoparticle therapeutics for intracerebral glioma. Neuro Oncol. 2017 Mar 1;19(3):372-382. doi: 10.1093/neuonc/now198.

 

Kim DG, Kim KH, Seo YJ, Yang H, Marcusson EG, Son E, Lee K, Sa JK, Lee HW, Nam DH. Anti-miR delivery strategies to bypass the blood-brain barrier in glioblastoma therapy. Oncotarget. 2016 May 17;7(20):29400-11. doi: 10.18632/oncotarget.8837.

 

Halle B, Thomassen M, Venkatesan R, Kaimal V, Marcusson EG, Munthe S, Sørensen MD, Aaberg-Jessen C, Jensen SS, Meyer M, Kruse TA, Christiansen H, Schmidt S, Mollenhauer J, Schulz MK, Andersen C, Kristensen BW. Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures.  J Neurooncol. 2016 Jul;128(3):395-404. doi: 10.1007/s11060-016-2125-x.

 

Teplyuk NM, Uhlmann EJ, Gabriely G, Volfovsky N, Wang Y, Teng J, Karmali P, Marcusson E, Peter M, Mohan A, Kraytsberg Y, Cialic R, Chiocca EA, Godlewski J, Tannous B, Krichevsky AM. Therapeutic potential of targeting microRNA-10b in established intracranial glioblastoma: first steps toward the clinic.  EMBO Mol Med. 2016 Feb 9;8(3):268-87.

 

Halle B, Marcusson EG, Aaberg-Jessen C, Jensen SS, Meyer M, Schulz MK, Andersen C, Kristensen BW. Convection-enhanced delivery of an anti-miR is well-tolerated, preserves anti-miR stability and causes efficient target de-repression: a proof of concept.  J Neurooncol. 2016 Jan;126(1):47-55.

 

Wong HK, Fatimy RE, Onodera C, Wei Z, Yi M, Mohan A, Gowrisankaran S, Karmali P, Marcusson E, Wakimoto H, Stephens R, Uhlmann EJ, Song JS, Tannous B, Krichevsky AM. The Cancer Genome Atlas analysis predicts microRNA for targeting cancer growth and vascularization in glioblastoma. Mol Ther. 2015 Apr 23. doi: 10.1038/mt.2015.72.

 

Teplyuk NM, Uhlmann EJ, Wong AH, Karmali P, Basu M, Gabriely G, Jain A, Wang Y, Chiocca EA, Stephens R, Marcusson E, Yi M, Krichevsky AM.MicroRNA-10b inhibition reduces E2F1-mediated transcription and miR-15/16 activity in glioblastoma. Oncotarget. 2015 Feb 28;6(6):3770-83.

 

Hogan DJ, Vincent TM, Fish S, Marcusson EG, Bhat B, Chau BN, Zisoulis DG. Anti-miRs competitively inhibit microRNAs in Argonaute complexes. PLoS One. 2014 Jul 3;9(7):e100951.

 

Zhou W, Fong MY, Yu Y, Chow C, Somlo G, Palomares MR, O’Connor STF, Chin AR, Marcusson EG, Chu P, Wu X, Li AX, Li Z, Ren X, Boldin M, Wang SE. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell, 2014 Apr 14;25(4):501-15.

 

Jin L, Wessely O, Marcusson EG, Ivan C, Calin G, Alahari S. Pro-oncogenic factors miR-23b- and miR-27b are regulated by Her2/Neu, EGF, and TNFα in breast cancer. Cancer Res. 2013 May 1;73(9):2884-96.

 

Lin R, Roychowdhury-Saha M, Black C, Watt AT, Marcusson EG, Freier SM, Edgington TS. Control of RNA processing by a large non-coding RNA over-expressed in carcinomas. FEBS Lett. 2011 Feb 18;585(4):671-6.

 

Carrasco RA, Stamm NB, Marcusson E, Sandusky G, Iversen P, Patel BK. Antisense inhibition of survivin expression as a cancer therapeutic. Mol Cancer Ther. 2011 Feb;10(2):221-32.

 

Huynh C, Segura MF, Gaziel-Sovran A, Menendez S, Darvishian F, Chiriboga L, Levin B, Meruelo D, Osman I, Zavadil J, Marcusson EG, Hernando E. Efficient in vivo microRNA targeting of liver metastasis. Oncogene. 2011 Mar 24;30(12):1481-8.

 

Elyakim E, Sitbon E, Faerman A, Tabak S, Montia E, Belanis L, Dov A, Marcusson EG, Bennett CF, Chajut A, Cohen D, Yerushalmi N. hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy. Cancer Res. 2010 Oct 15;70(20):8077-87.

 

Swarbrick A, Woods SL, Shaw A, Balakrishnan A, Phua Y, Nguyen A, Chanthery Y, Lim L, Ashton LJ, Judson RL, Huskey N, Blelloch R, Haber M, Norris MD, Lengyel P, Hackett CS, Preiss T, Chetcuti A, Sullivan CS, Marcusson EG, Weiss W, L’Etoile N, Goga A. miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma. Nat Med. 2010 Oct;16(10):1134-40.

 

Nannuru KC, Futakuchi M, Varney ML, Vincent TM, Marcusson EG, Singh RK. Matrix metalloproteinase (MMP)-13 regulates mammary tumor-induced osteolysis by activating MMP9 and transforming growth factor-beta signaling at the tumor-bone interface. Cancer Res. 2010 May 1;70(9):3494-504.

 

Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW, Weinberg RA. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 2010 Apr;28(4):341-7.

 

Nannuru KC, Futakuchi M, Sadanandam A, Wilson TJ, Varney ML, Myers KJ, Li X, Marcusson EG, Singh RK. Enhanced expression and shedding of receptor activator of NF-kappaB ligand during tumor-bone interaction potentiates mammary tumor-induced osteolysis. Clin Exp Metastasis. 2009;26(7):797-808.

 

Ernst M, Najdovska M, Grail D, Lundgren-May T, Buchert M, Tye H, Matthews VB, Armes J, Bhathal PS, Hughes NR, Marcusson EG, Karras JG, Na S, Sedgwick JD, Hertzog PJ, Jenkins BJ. STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J. of Clin. Invest. 2008 May 1;118(5):1727-1738.

 

GraffJR, KonicekBW, Carter JH, Marcusson EG. Targeting the eukaryotic translation initiation factor 4E (eIF4E) for cancer therapy. Cancer Res. 2008 Feb 1;68(3):631-4.

Graff JR, Konicek BW, Vincent TM, Lynch RL, Monteith D, Weir SN, Schwier P, Capen A, Goode RL, Dowless MS, Chen Y, Zhang H, Sissons S, Cox K, McNulty AM, Parsons SH, Wang T, Sams L, Geeganage S, Douglass LE, Neubauer BL, Dean NM, Blanchard K, Shou J, Stancato LF, Carter JH, Marcusson EG. Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity. J Clin Invest. 2007 Sep;117(9):2638-48.

Low J, Huang S, Dowless M, Blosser W, Higgs R, Vincent TM, Davis S, Hodgson J, Koller E, Marcusson EG, Blanchard K, Stancato L.  Statistical analysis of knockdown effects of validated siRNAs and antisense oligonucleotides using high-content imaging. J. of Biomolecular Screening. 2007 Sep;12(6):775-88.

 

Kim Y, Yoon JW, Xiao X, Dean NM, Monia BP, Marcusson EG.  Selective downregulation of glioma-associated oncogene 2 (Gli2) inhibits the proliferation of hepatocellular carcinoma cells. Cancer Res. 2007 Apr 15;67(8):3583-93.

 

Habens F, Lapham AS, Dallman CL, Pickering BM, Michels J, Marcusson EG, Johnson PW, Packham G. Distinct promoters mediate constitutive and inducible Bcl-X(L) expression in malignant lymphocytes. Oncogene. 2007 Mar 22;26(13):1910-9.

 

Koller E, Propp S, Murray H, Lima W, Bhat B, Prakash TP, Allerson CW, Swayze EE, Marcusson EG, Dean NM.  Competition for RISC binding predicts in vitro potency of siRNA. Nucleic Acids Res. 2006;34(16):4467-76.

 

Perera RJ, Marcusson EG, Koo S, Kang X, Kim Y, White N, Dean NM.   Identification of novel PPARg target genes in primary human adipocytes. Gene. 2006 Mar 15;369:90-9.

 

Esau E, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, Sun Y, Koo S, Perera RJ, Jain R, Dean NM, Freier SM, Bennett CF, Lollo B, Griffey R.  MicroRNA-143 regulates adipocyte differenetiation. J Biol Chem. 2004;279: 52361-52365.

 

Henry SP, Marcusson EG, Vincent TM, Dean NM.  Setting sights on the treatment of ocular angiogenesis using antisense oligonucleotides. Trends Pharmacol Sci.  2004 Oct; 25(10):523-27.

 

Marcusson EG, Vincent TM, Hari KL, Chiang MY, Dean NM.  Case study: use of a library of antisense inhibitors for gene functionalization and drug target validation. Drug Discovery Today: TARGETS. 2004 Jun; 3(3): 117-22.

 

Michels J, O’Neill JW, Dallman CL, Mouzakiti A, Habens F, Brimmell M, Zhang KY, Craig RW, Marcusson EG, Johnson PW, Packham G.  Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to a cell death molecule by efficient caspase-mediated cleavage. Oncogene. 2004 Jun 17;23(28):4818-27.

 

Ravichandran LV, Dean NM, Marcusson EG. Use of antisense oligonucleotides in functional genomics and target validation. Oligonucleotides. 2004 Spring;14(1): 49-64.

 

Beger C, Pierce LN, Kruger M, Marcusson EG, Robbins JM, Welcsh P, Welch PJ, Welte K, King MC, Barber JR, Wong-Staal F.  Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach. Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):130-5.

 

Welch PJ, Marcusson EG, Li QX, Zhou C, Beger C, Krueger M, Barber J.  Identification and validation of a potential human tumor suppressor gene using a library of randomized hairpin ribozymes.  Genomics. 2000 Jun 15;66(3):274-83.

 

Taylor JK, Zhang QQ, Monia BP, Marcusson EG, Dean NM.  Inhibiton of Bcl-XL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli. Oncogene. 1999 Aug 5;18(31):4495-504.

 

Marcusson, EG, Yacyshyn BR, Shanahan W, Dean NM.  Preclinical and clinical pharmacology of antisense oligonucleotides. Mol Biotechnol. 1999 Aug;12(1):1-11.

 

Marcusson EG, Bhat B, Manoharan M, Bennett C F, Dean NM. Phosphorothioate oligodeoxynucleotides dissociate from cationic lipids before entering the nucleus. Nucleic Acids Res. 1998; 26, 2016-2023.

 

Seaman MN, Marcusson E G, Cereghino JL, Emr SD.  Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products. J Cell Biol. 1997; 137, 79-92.

 

Westphal V, Marcusson EG, Winther JR, Emr SD, van den Hazel HB. Multiple pathways for vacuolar sorting of yeast proteinase A. J Biol Chem. 1996; 271, 11865-70.

 

Cereghino JL, Marcusson EG, Emr SD. The cytoplasmic tail domain of the vacuolar protein sorting receptor Vps10p and a subset of VPS gene products regulate receptor stability, function, and localization. Mol Biol Cell. 1995; 6, 1089-102.

 

Stack JH, Herman PK, DeWald DB, Marcusson EG, Lin Cereghino J, Horazdovsky BF, Emr SD.  Novel protein kinase/phosphatidylinositol 3-kinase complex essential for receptor-mediated protein sorting to the vacuole in yeast. Cold Spring Harb Symp Quant Biol. 1995; 60, 157-70.

 

Marcusson EG, Horazdovsky BF, Cereghino JL, Gharakhanian E, Emr SD.  The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene. Cell. 1994; 77, 579-86.

 

Schnaper HW, Cottel J, Merrill S, Marcusson E, Kissane JM, Shackelford GD, So SK, Nelson RD, Cole BR, Smith ML, and et al. Early occurrence of end-stage renal disease in a patient with infantile nephropathic cystinosis. J Pediatr.  1992; 120, 575-8.

 

Greene AA, Marcusson EG, Morell GP, Schneider JA. Characterization of the lysosomal cystine transport system in mouse L- 929 fibroblasts. J Biol Chem. 1990; 265, 9888-95.

 

Smith ML, Clark KF, Davis SE, Greene AA, Marcusson EG, Chen YJ, Schneider JA.  Diagnosis of cystinosis with use of placenta [letter]. N Engl J Med. 1989; 321, 397-8.