Russell J. Howard

Russell J. Howard is an Australian-born scientist, CEO and entrepreneur. He was a pioneer in the fields of molecular parasitology, especially malaria,[2] and in leading the commercialisation of one of the most important methods used widely today in molecular biology today called “DNA shuffling" or "Molecular breeding",[3] a form of "Directed evolution".

Russell J. Howard
Born
Australia
NationalityAustralian
Known forMalaria Research, Biotechnology Industry
AwardsAdvance Global Australian Award, Overall winner and Biotechnology Award, 2013[1]
Scientific career
FieldsBiotechnology
InstitutionsNIH, Maxygen, Affymax, Oakbio, Circadian, Prima Biomed, NeuClone, Garvan Institute of Medical Research

His contributions to malaria research over an 18-year period began in Australia at the Walter and Eliza Hall Institute of Medical Research, then continued as a tenured Principal Investigator at the National Institutes of Health(NIH) in Bethesda, MD, USA, and continued at the biotechnology companies DNAX (now Schering-Plough Biopharma) and Affymax in California. Thirteen years of his group's malaria research on antigenic variation in malaria[2][4] culminated in the first molecular cloning of the malarial antigen PfEMP1,[5] a parasite protein that this human malaria parasite expresses on the surface of malaria-infected red cells[6] This antigen represents critical biological functions for the parasite including immune evasion and adherence to microvascular endothelial cells.[7] During this time Howard served on the World Health Organization's Special Program for Research and Training in Tropical Diseases and the USAID program for research and vaccine development in malaria.

While Howard was President and Scientific Director at Affymax Research Institute, Willem 'Pim' Stemmer[8] conceived and developed DNA shuffling Technology.[3] This revolutionary technology for improving the expressed phenotype of genes, pathways, plasmids, viruses and genomes gave birth to the creation and spinout of Maxygen Inc.[9] where Howard was CEO for 12 years. He took the company public[10] and led its growth with 10s of corporate partnerships, technology application programs that led ultimately to the development and commercialisation worldwide of 10s of Life Science products in diverse fields. Maxygen exploited DNA Shuffling technology across the entire Life Sciences spectrum, creating new companies dedicated to Agricultural Products (Verdia[11]) and Industrial Chemical opportunities (Codexis[12]) as well as a Protein Pharmaceuticals Business (Perseid[13]).

In 2008, Howard left Maxygen to found Oakbio Inc. He is currently a founder and the CEO of Oakbio Inc. in Sunnyvale, California, USA, a company designing microbes for production of cost-competitive chemicals using industrial CO2 emissions as carbon source . Additionally, he is currently Commercial Strategy Advisor at the Garvan Institute of Medical Research's Kinghorn Centre for Clinical Genomics.[14][15]

Howard has published over 145 scientific publications in refereed journals and is an inventor on nine issued patents.

Education

Howard graduated from Box Hill High School in Melbourne, Australia and later studied Chemistry and Biochemistry at the University of Melbourne, culminating in a PhD in 1975 where he studied the carbohydrate and central metabolism of Caulerpa simpliciuscula, a marine green alga.

Employment

He spent his first postdoctoral studies from 1976–1979 at the Immunoparasitology Laboratory at the Walter & Eliza Hall Institute in Melbourne, with frequent visits and collaborative work on sialic acids at the Biochemisches Institut at Christian Albrechts Universitat in Kiel, Germany. He started working as a Research Associate in the Malaria Section of the National Institutes of Health in Bethesda, Maryland before earning his tenure in the same institution in 1987. From 1988 to 1992, he worked at the Laboratory of Infectious Diseases of the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto, California, USA, with dual roles, studying cytokine genes for Schering Plough, the parent organisation of DNAX Research Institute, and leading his Infectious Diseases laboratory there on malaria work funded by DNAX and USAID.

In 1994, he was named President and Scientific Director of Affymax, Inc. where he managed teams working on small molecule drug lead discovery using combinatorial chemistry and high throughput target screening. His independent malaria work continued at Affymax with support from USAID and Affymax, leading to cloning of the PfEMP1 gene while at Affymax.[5] After Affymax was purchased by GlaxoWellcome, Howard led technology transfer and interchange in combinatorial chemistry, drug discovery and optimisation between Affymax and GlaxoWellcome worldwide. During this time, Molecular breeding or DNA shuffling Technology was conceived[3] and the nascent company Maxygen Inc. incubated for later spun out from Affymax-GlaxoWellcome.[9]

From 1997 to 2009, Howard worked as Maxygen's CEO, focusing on human, including, protein pharmaceutical drugs and vaccine discovery, as core business. Non-core businesses were successively incubated, nurtured and spun-out (Codexis[12]) or sold (Verdia[11]). In 2008, he left Maxygen with $200MM in cash, no debt, on-going clinical stage drug development programs and multiple partnerships and licenses with other parties. Following his departure, Howard started Oakbio, Inc., a seed-stage, privately held Clean Technology company in Sunnyvale, California, USA[www.oakbio.com]. Oakbio captures CO2 from industrial waste gas streams and uses microbial chemosynthetic systems to capture and convert this carbon resource to valuable chemicals, sequestering a Green House Gas from accumulation in the atmosphere.

In 2012 Howard moved residency from Silicon Valley, California, where he had worked for 25 years, to Sydney, Australia.

In 2013 he joined the Garvan Institute of Medical Research's Kinghorn Centre for Clinical Genomics as Commercial Strategy Advisor. He is now the Head of Commercial Strategy, The Kinghorn Centre for Clinical Genomics. In addition, currently Howard is Executive Chairman at NeuClone Pty. Ltd, Sydney, developing biosimilar monoclonal antibody products and a Non Executive Director at Immutep[16] (a biotechnology company working in the field of cancer immunotherapy).

Financing leadership

With Howard as CEO, Maxygen, Inc. completed its Initial Public Offering of $110MM in 1999, just two years after its spinout from Affymax-GlaxoWellcome.[10] In March 2000, Maxygen raised another $150MM in a Secondary Public Offering. More recently, Howard and colleagues at NeuClone, Pty. Ltd. raised >$10 MM (AUS) from private investors in Sydney to support development of a portfolio of 10 biosimilar monoclonal antibodies.

Recognition & research

Howard has been awarded three Doctor of Science (honoris causa) degrees, one from the University of Technology, Sydney, Australia in 2004, one from the University of Queensland, Brisbane, Australia in 2008 and the third from the University of Melbourne, Melbourne, Australia in 2014. Howard's >145 publications tackle topics ranging from the metabolism of the algae Caulerpa simpliciuscula, to the molecular pathogenesis of human cerebral malaria and the role of parasite antigenic variation and infected cell adherence in disease virulence. His papers reflect successful use of the tools of biochemistry, protein chemistry and structure-function, molecular biology, cell biology, large animal studies, and field studies with humans.

Patents

Howard is an inventor on nine patents. At the NIH he patented discovery, characterisation and cloning of a novel gene encoding a soluble malarial antigen, called PfHRP2[17] that the most lethal human malaria releases into the blood. This discovery led to a rapid, sensitive, inexpensive and reliable diagnostic test for malaria infection that the NIH licensed commercially.[18] This test has been used worldwide for over 15 years.[19] In 1990 and 1995, he and his colleagues at Affymax applied for the patents of antigenic determinants obtained using a pathogenic agent or a derivative that presents a restricted set of antigens, and recombinant DNA clone from Plasmodium falciparum. While working at Maxygen Inc., he and his colleagues developed three patents for the following technologies: antigen library immunisation using polynucleotides encoding flavivirus and alphavirus; multivalent antigenic polypeptides; and optimisation of immunomodulatory properties of genetic vaccines

Selected references and publications
  2. Howard, Russell J. (1982). "Alterations in the Surface Membrane of Red Blood Cells During Malaria". Immunological Reviews. 61: 67–107. doi:10.1111/j.1600-065X.1982.tb00374.x. PMID 6174414.
     • http://www.pnas.org/content/80/13/4129.short Howard, R.J., Barnwell, J.W., and Kao, V.: Antigenic variation in Plasmodium knowlesi malaria: Identification of the variant antigen on infected erythrocytes. Proc. Natl. Acad. Sci. USA 80: 4129–4133, 1983.
     • http://jem.rupress.org/content/159/6/1567.abstract Leech, J.H., Barnwell, J.W., Miller, L.H., and Howard, R.J.: Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum infected erythrocytes. J. Exp. Med. 159:1567–1575, 1984.
     • Howard, R.J.: Antigenic variation of blood stage malaria parasites. Phil. Trans. R. Soc. Lond. B 307: 141–158, 1984.
     • http://jem.rupress.org/content/160/5/1585.abstract Aley, S.B., Sherwood, J.A., and Howard, R.J.: Knob-positive and knob-negative Plasmodium falciparum differ in expression of a strain- specific malarial antigen on the surface of infected erythrocytes. J. Exp. Med. 160: 1585–1590, 1984.
  3. Stemmer, W.P.C. (2002). "Molecular Breeding of Genes, Pathways and Genomes by DNA Shuffling". Biotechnol. Bioprocess Eng. 7: 121–129. doi:10.1016/S1381-1177(02)00146-7.
  4. Leech, J.H., Barnwell, J.W., Aikawa, M., Miller, L.H., and Howard, R.J.: Plasmodium falciparum malaria: Association of knobs on the surface of infected red cells with a histidine-rich protein and the red cell skeleton. J. Cell Biol. 98: 1256–1264, 1984.
     • http://www.sciencemag.org/content/231/4734/150.short 65. Marsh, K., and Howard, R.J.: Antigens induced on erythrocytes by natural Plasmodium falciparum infections: Expression of antigenically diverse and conserved determinants. Science 231: 150–153, 1986.
     • http://jcb.rupress.org/content/104/5/1269.abstract Howard, R.J., Lyon, J., Uni, S., Saul, A.J., Aley, S.B., Klotz, F., Panton, L.J., Sherwood, J.A., Marsh, K., Aikawa, M., Rock, E.P.: Transport of a Mr ~300,000 Plasmodium falciparum protein (PfEMP2) from the intraerythrocytic parasite to the cytoplasmic face of the host cell membrane. J. Cell Biol. 104: 1269–1280, 1987.
     • http://www.sciencemag.org/content/234/4782/1349.short Miller, L.H., Howard, R.J., Carter, R., Good, M.F., Nussenzweig, V. and Nussenzweig, R.S.: Research towards malaria vaccines. Science 234: 1349–1356,1987.
     • http://cat.inist.fr/?aModele=afficheN&cpsidt=7332277 Howard, R.J. Malaria: The search for vaccine antigens and new chemotherapeutic strategies. Blood 74: 533–536, 1989.
     • Molecular studies related to the pathogenesis of cerebral malaria.
     • http://bloodjournal.hematologylibrary.org/content/78/1/226.short van Schravendijk, M.R., Rock, E.P., Marsh, K., Ito, Y., H., Aikawa, M., Neequaye, J., Ofori-Adjei, D., Rodriguez, R., Patarroyo, M.E. and Howard, R.J.: Characterization and localization of Plasmodium falciparum surface antigens on infected erythrocytes from West African patients. Blood 78: 226–236, 1991.
     • http://www.jbc.org/content/267/25/18244.short Leung, L.L., Li W-X., McGregor, J.L., Albrecht, G.R. and Howard, R.J.: CD36 peptides enhance or inhibit CD36-Thrombospondin binding. A two-step process of ligand-receptor interaction. J. Biol. Chem. 267: 18244-18250,1992.
     • http://bloodjournal.hematologylibrary.org/content/80/8/2097.short Handunnetti, S.M., van Schravendijk, M.-R., Hasler, T.H., Barnwell, J.W., Greenwalt, D.E. and Howard, R.J.: Involvement of CD36 on erythrocytes as a rosetting receptor for Plasmodium falciparum-infected erythrocytes. Blood. 80: 2097–2104,1992.
     • Howard, R. J. Asexual deviants take over. Nature, 357: 647–648, 1992.
     • Howard, R. J. and Pasloske, B.L. Target antigens for asexual malaria vaccine development. Parasitology Today, 9: 369–372, 1993.
     • http://www.annualreviews.org/doi/pdf/10.1146/annurev.med.45.1.283 Pasloske, B. L. and Howard, R. J., Malaria, the red cell, and the endothelium. Annu. Rev. Med. 45: 283–295, 1994.
  5. Baruch, Dror I.; Pasloske, Britten L.; Singh, Hardeep B.; Bi, Xiahui; Ma, Xin C.; Feldman, Michael; Taraschi, Theodore F.; Howard, Russell J. (1995). "Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes". Cell. 82 (1): 77–87. doi:10.1016/0092-8674(95)90054-3. PMID 7541722.
  6. Leech, J.H., Barnwell, J.W., Miller, L.H., and Howard, R.J.: Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum infected erythrocytes. J. Exp. Med. 159:1567–1575, 1984.
     • Howard, R.J.: Antigenic variation of blood stage malaria parasites. Phil. Trans. R. Soc. Lond. B307: 141–158, 1984.
     • http://jem.rupress.org/content/160/5/1585.abstract.
  7. Baruch, D. I.; Ma, X. C.; Singh, H. B.; Bi, X.; Pasloske, B. L.; Howard, R. J. (1997). "Identification of a region of PfEMP1 that mediates adherence of Plasmodium falciparum infected erythrocytes to CD36: conserved function with variant sequence". Blood. 90 (9): 3766–3775. doi:10.1182/blood.V90.9.3766. PMID 9345064.
  8. Willem P.C. Stemmer
  9. Zaffaroni Announces New Start-Up Company – Maxygen, Inc.
  10. Maxygen, Inc. Raises $110 Million In Initial Public Offering of Its Common Stock
  11. DuPont To Acquire Maxygen Subsidiary Verdia
  12. Maxygen Announces Launch of Wholly Owned Chemicals Subsidiary, Codexis, Inc.
  13. Maxygen and Astellas Announce Global Agreement to Develop New Therapies for Autoimmune Diseases and Transplantation.
  14. "Kinghorn Centre for Clinical Genomics Staff". Organisation Website. Garvan Institute. Retrieved 21 February 2014.
  15. Durkin, Patrick. "Russell Howard: scientist, entrepreneur, CEO". Magazine. Australian Financial Review. Retrieved 21 February 2014.
  16. "Russell Howard, Ph.D." www.immutep.com. Retrieved 9 December 2019.
  17. Howard, R.J.; Uni, S.; Aikawa, M.; Aley, S.B.; Leech, J.H.; Lew, A.M.; Wellems, T.E.; Marsh, K.; Rener, J.; Taylor, D.W. (1986). "Secretion of a malarial histidine-rich protein (Pf HRP II) from Plasmodium falciparum infected erythrocytes". J. Cell Biol. 103 (4): 1269–1277. doi:10.1083/jcb.103.4.1269. PMC 2114335. PMID 3533951.
  18. Wellems, T.E.; Howard, R.J. (1986). "Homologous genes encode two distinct histidine-rich proteins in a cloned isolate of Plasmodium falciparum". Proc. Natl. Acad. Sci. USA. 83 (16): 6065–6069. doi:10.1073/pnas.83.16.6065. PMC 386439. PMID 3016741.
  19. Rapid Diagnostic Test Information: Malaria Diagnostic Overview. Archived 10 May 2009 at the Wayback Machine
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