Founder

More about Michael L. Metzker, Ph.D.

I invented the TRC technology (US Patent Application Number 15/614,958 to be issued April 12, 2022 and European patent number 17 731 374.9 granted in January 2022), have received one R43 grant award for the detection of miRNAs using TRCs in pancreatic cancer (R43 CA200398-01A1), and will lead this phase I proposal. Having been an innovator for 30 years, I have focused my research in three areas: next-generation sequencing (NGS) technology development, exploration of the role of sequence variation in diabetes, and the study of HIV-1 transmission between individuals. In addition to my publications listed below, I am an inventor on 52 issued patents and patent applications. My interests also include entrepreneurship, having started my first company, LaserGen, Inc. in 2002. LaserGen’s primary focus is development of novel reversible terminators for NGS applications (see most relevant publications). In collaboration with the scientific team at LaserGen, I developed a number of diverse, structurally-related reversible terminators, which have led to the issuance of U.S. patents including U.S. Patent Nos. 7,893,227; 7,897,737; 7,964,352; 8,148,503; 8,198,029; 8,361,727; 8,497,360; 8,877,905; 8,889,860; 8,969,535; 9,200,319; 9,399,798; 10,041,115; and 11,001,886. After 14 years in academia, I have transitioned into an adjunct associate professor position at BCM to start a new corporate venture, RedVault Biosciences. Our mission is to identify technological opportunities, provide innovative solutions, and further advance the field of genomic medicine. Our approach differs from a traditional business model, which takes an idea from bench to marketplace. At RedVault, our mission is to define a need in the field, develop innovative solutions, reduce the idea to practice by demonstrating proof-ofconcept, pursue peer-review publications of promising technological results, develop a strong intellectual property portfolio, and identify strategic corporate partnerships that provide licensing or acquisition opportunities for product commercialization. Our R43 grant proposes demonstrating technical feasibility of our long template approach, see US patent application 2017-0349939 A1, with using Illumina technology.

1. Metzker ML (2010) Sequencing technologies ― the next generation. Nature Rev. Genet. 11:31-46. PMID:19997069 (No PMCID available).

2. Metzker, ML (2009) Sequencing in real time. Nature Biotechnol. 27:150-151.

3. Metzker ML (2005) Emerging Technologies in DNA Sequencing. Genome Res. 15:1767-1776.

B. Positions and Honors

1983-to-1984 Laboratory Technician, Aerojet-General Corporation, Sacramento, CA

1984-to-1987 Research Chemist, Bio-Rad Laboratories, Richmond, CA

1987-to-1991 Associate Scientist, Applied Biosystems, Inc., Foster City, CA

1996-to-1999 Senior Research Biologist, Merck Research Laboratories, West Point, PA

1999-to-2008 Assistant Professor, Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX

2001-to-2009 Adjunct Assistant Professor, Department of Chemistry, Rice University, Houston, TX

2002-to-2012 Founder, President & CEO, LaserGen, Inc.

2003-to-2006 Editorial Board, Genome Research, Cold Spring Harbor Laboratory Press

2005-to-2007 Permanent member of NIH Instrumentation and Systems Development (ISD) study section; NIBIB

2006-to-2012 Advances in Genome Biology & Technology Meeting, Scientific Advisor

2006-to-Present Ad hoc reviewer to NIH: NCI, NIDDK, NIBIB, NHGRI, and NICHD Study Sections

2007-to-Present Ad hoc reviewer to Genome Canada, CIHR, and Terry Fox Foundation Study Sections

2011-to-2013 Genome Canada: Advancing Technology Innovation through Discovery (ATID) Advisory Committee

2007-to-Present Milestones in DNA Technologies, Nature, Scientific Advisor

2009-to-2014 Associate Professor, Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX

2009-to-2019 Adjunct Associate Professor, Department of Chemistry, Rice University, Houston, TX

2013-to-Present Founder, President & CEO, RedVault Biosciences, LP

2014-to-2019 Adjunct Associate Professor, Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX

2018-to-Present College of Reviewers, Canadian Institutes of Health Research

C. Contributions to Science

My contributions to science have involved large-scale genomic science projects including the human genome project, several mammalian and insect genome projects, and the 1,000 genomes project.

1. Bouck JB, Metzker ML, and Gibbs RA (2000) Shotgun sample sequence comparisons between mouse and human genomes. Nature Genet. 25:31-33.

2. International Human Genome Sequencing Consortium: Baylor College of Medicine Human Genome Sequencing Center: Gibbs RA, Muzny DM Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, and Weinstock GM (2001) Initial sequencing and analysis of the human genome. Nature 409:860-921.

3. Gibbs RA, Weinstock GM, Metzker ML et al. (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428:493-521.

4. Richards S et al. (2005) Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution. Genome Res. 15:1-18.

5. Ross MT et al. (2005) The DNA sequence of the human X chromosome. Nature 434:325-337.

6. Scherer S et al. (2006) The Finished DNA Sequence of Human Chromosome 12. Nature 440 346-351.

7. Muzny D et al. (2006) The DNA sequence, annotation and analysis of human chromosome 3. Nature 440:1194-1198.

8. Church DM et al. (2009) Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 5:e1000112.

9. The 1000 Genomes Project Consortium. (2010) A map of human genome variation from population-scale sequencing. Nature 467:1061-73.

10. Sudmant et al. Diversity of human copy number variation and multicopy genes. (2010) Science 330:641-646.

11. Mills et al. Mapping copy number variation by population-scale genome sequencing. (2011) Nature, 470:59-65.

12. Danecek et al. (2011) The variant call format and VCFtools. Bioinformatics, 27:2156-2158.

13. Conrad et al., (2011) Variation in genome-wide mutation rates within and between human families. Nature Genet. 43:712-714.

14. Gravel et al. (2011) Demographic history and rare allele sharing among human populations. Proc. Natl. Acad. Sci. USA. 108: 11983-11988.

15. Marth et al. (2011) The functional spectrum of low-frequency coding variation. Genome Biol. 12:R84.

16. Clarke et al. (2012) The 1000 genomes project: data management and community access. Nature Methods, 9:459-462.

My contributions to science have also been focused in the area of technology development of genomic analysis platforms and methods:

1. Metzker ML, Raghavachari R, Richards S, Civitello A, Burgess K, and Gibbs RA (1994) Termination of DNA synthesis by novel 3’-modified-deoxyribonucleoside 5’-triphosphates, Nucleic Acids Res. 22, 4259-4267.

2. Metzker ML, Allain KM, and Gibbs RA (1995) Accurate determination of DNA in agarose gels using the novel algorithm GelScann(1.0), Comput. Applic. Biosci. 11, 187-194.

3. Metzker ML, Lu J and Gibbs RA (1996) Electrophoretically Uniform Fluorescent Dyes for Automated DNA Sequencing, Science 271: 1420-1422.

4. Metzker ML, Ansari-Lari MA Liu XL, Holder DJ, and Gibbs RA (1998) Quantitation of Mixed-Base Populations of HIV-1 Variants by Automated DNA Sequencing with BODIPY Dye-Labeled Primers. BioTechniques 25:446-462.

5. Metzker ML, Raghavachari R, Burgess K, and Gibbs RA (1998) Elimination of residual natural nucleotides from 3’-O-modified-dNTP syntheses by enzymatic Mop-Up. BioTechniques 25:814-817.

6. Muzny DM, Metzker ML, Bouck J, Gorrell JH, Ding Y, Maxim E, and Gibbs RA (1998) Using BODIPY Dye-Primer Chemistry in Large-Scale Sequencing. IEEE Engineering in Medicine and Biology 88-93.

7. Dederich DA, Okwuonu G, Garner T, Denn A, Sutton A, Escotto M, Martindale A, Delgado O, Muzny DM, Gibbs RA and Metzker ML (2002) Glass Bead Purification of Plasmid Template DNA for High-Throughput Sequencing of Mammalian Genomes. Nucleic Acids Res. 30:e32.

8. Thoresen LH, Jiao GS, Haaland WC, Metzker ML, and Burgess K (2003) Rigid, Conjugated Fluoresceinated Thymidine Triphosphates: Syntheses and Polymerase Mediated Incorporation Into DNA. Chem. Eur. J. 9:4603-4610.

9. Lewis EK, Haaland WC, Nguyen F, Heller DA, Allen MJ, Macgregor RR, Berger CS, Willingham B, Burns LA, Scott GB, Kittrell C, Johnson BR, Curl RF, Metzker ML (2005) Color-blind fluorescence detection for four-color DNA sequencing Proc. Natl. Acad. Sci. USA 102:5346-5351.

10. Jiao G-S, Thoresen LH, KimTG, Haaland WC, Topp MR, Hochstrasser RM, Metzker ML, Burgess K (2006) Syntheses, photophysical properties, and applications of through-bond energy transfer cassettes for multiplexing in biotechnology. Eur. J. Chem. 12:7816-7826.

11. Wu W, Stupi BP, Litosh VA, Mansouri D, Farley D, Morris S, Metzker S, Metzker ML (2007) Termination of DNA synthesis by N6-alkylated, not 3’-O-alkylated, photocleavable 2’-deoxyadenosine triphosphates. Nucleic Acids Res. 35:6339-6349.

12. Litosh VA, Wu W, Stupi BP, Wang J, Morris, SE, Hersh MN, Metzker ML. (2011) Improved nucleotide selectivity and termination of 3'-OH unblocked reversible terminators by molecular tuning of 2- nitrobenzyl alkylated HOMedU triphosphates. Nucleic Acids Res. 39:e39.

13. Stupi BP, Li H, Wang J, Wu W, Morris SE, Litosh VA, Muniz J, Hersh MN, Metzker ML. (2012) Stereochemistry of benzylic carbon substitution coupled with ring modification of 2-nitrobenzyl groups as key determinants for fast-cleaving reversible terminators. Angew. Chem. Int. Ed., 51: 1724-1727.

14. Gardner AF, Wang J, Wu W, Karouby J, Li H, Stupi BS, Jack WE, Hersh MN, Metzker ML (2012) Improved fidelity and rapid incorporation kinetics of 3’-OH unblocked reversible terminators by Therminator DNA polymerase. Nucleic Acids Res., 40:7404-7415.

My contributions to science have also focused on the area of gene discovery and sequence variation studies with emphasis in diabetes:

1. Ansari-Lari MA, Liu XM, Metzker ML, Rut AR and Gibbs RA (1997) The extent of genetic variation in the CCR5 gene. Nature Genet. 16: 221-222.

2. Petrukhin K, Koisti MJ, Bakall B, Li W, Xie G, Marknell T, Sandgren O, Forsman K, Holmgren G, Andreasson, S Vujic, M Bergen AAB, McGarty-Dugan V, Figueroa D, Austin CP, Metzker ML, Caskey CT, and Wadelius C (1998) Identification of the gene responsible for Best macular dystrophy. Nature Genet. 19:241-247.

3. Hey PJ, Twells RCJ, Phillips MS, Nakagawa Y, Brown SD, Kawaguchi Y, Cox R, Xie G, Dugan V, Hammond H, Metzker ML, Todd JA, and Hess JF (1998) Cloning of a novel member of the lowdensity lipoprotein receptor family. Gene 216:103-111.

4. Brown SD, Twells RCJ, Hey PJ, Cox RD, Levy ER, Soderman AR, Metzker ML, Caskey CT, Todd JA, and Hess JF (1998) Isolation and characterization of LRP6, a novel member of the low-density lipoprotein receptor gene family. Biochem. Biophys. Res. Commun. 248:879-888.

5. Allikmets R, Seddon JM, Bernstein PS, Hutchinson A, Sharma S, Gerrard B, Li W, Metzker ML Wadelius C, Caskey CT, Dean M, and Petrukhin K (1999) Rare variants of the best disease gene in patients with age-related macular degeneration and other maculopathies. Hum. Genet. 104: 449-453.

6. Bai C, Connolly B, Liu X, Hilliard CA, Galloway SM, Sandig V, Liu Q, Metzker ML, Austin CP, and Caskey CT (2000). Overexpression of a new secreted member of tumor necrosis factor receptor family in gastrointestinal tract tumors. Proc. Natl. Acad. Sci. USA 97:1230-1235.

7. V, Youil R, Bett AJ, Franlin LL, Oshima M, Maione D, Wang F, Metzker ML, Savino R, Caskey CT (2000) Optimization of the helper-dependent adenovirus system for production and potency in vivo. Proc. Natl. Acad. Sci. USA. 97:1002-1007.

8. Zhang K, Kniazeva M, Han M, Li W, Yu Z, Yang Z, Li Y, Metzker ML, Allikmets R, Zack DJ, Kakuk LE, Lagali PS, Wong PW, MacDonald IM, Sieving PA, Figueroa DJ, Austin CP, Gould RJ, Ayyagari R, and Petrukhin K (2001) A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Nature Genet. 27:89-93.

9. Twells RC, Metzker ML, Brown SD, Cox R, Garey C, Hammond H, Hey PJ, Levy E, Nakagawa Y, Philips MS, Todd JA, and Hess JF. (2001) The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13. Genomics 72:231-242.

10. Twells RCJ, Mein CA, Payne F, Veijola R, Gilbey M, Bright M, Timms A, Nakagawa Y, Snook H, Nutland S, Rance HE, Carr P, Dudbridge F, Cordell HJ, Cooper J, Tuomilehto-Wolf E, Tuomilehto J, Phillips M, Metzker ML, Hess JF, Todd JA (2003) Linkage and association mapping of the LRP5 locus on chromosome 11q13 in type 1 diabetes. Human Genet. 113:99-105.

11. Ueda H et al. (2003) Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423:506-511.

12. Twells RCJ, Mein CA, Phillips MS, Hess JF, Veijola R, Gilbey M, Bright M, Metzker ML, Lie BA, Kingsnorth A, Gregory E, Nakagawa Y, Snook H, Wang WYS, Masters J, Johnson G, Eaves I, Howson JMM, Clayton D, Cordell HJ, Nutland S, Rance H, Carr P and Todd JA (2003) Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene. Genome Res. 13:845-855.

13. Fernandez R, Zhang Y, Pai S, Metzker ML, Schumacher A (2005) l7Rn6 encodes a novel protein required for Clara cell function in mouse lung development. Genetics 172:389-399.

14. Haaland WC, Scaduto DI, Maldonado, MR, Mansouri DL, Nalini R, Iyer D, Patel S, Guthikonda A, Hampe CS, Balasubramanyam A, Metzker ML. (2009) The “A-β-” subtype of Ketosis-Prone Diabetes (KPD) is not predominantly a monogenic diabetic syndrome. Diabetes Care 32:873-877.

15. Redondo MJ, Muniz J, Rodriguez LM, Iyer D, Vaziri-Sani F, Haymond MW, Hampe CS, Metzker ML, Grant SFA, Balasubramanyam A. (2014) Association of TCF7L2 Variation with Single Islet Autoantibody Expression in Children with Type 1 Diabetes. BMJ Open Diabetes Res. Care, 2:e000008.

My contributions to science have focused on methods development and sequencing applications in HIV forensics.

1. Metzker ML, Mindell DP, Ptak RG, Gibbs RA, and Hillis DM (2002) Molecular Evidence of HIV-1 Transmission in a Louisiana Criminal Case. Proc. Natl. Acad. Sci. USA 99:14292-14297.

2. Scaduto DI, Brown JM, Haaland WC, Zwickl DJ, Hillis DM, Metzker ML. (2010) Source identification in two criminal cases using phylogenetic analysis of HIV-1 DNA sequences. Proc Natl Acad Sci USA 107:21242-21247.

3. Leitner, T. Metzker ML, et al., (2011) Guideline for HIV in court. Nature 473:284.

4. Doyle VP, Andersen JJ, Nelson BJ, Metzker ML, Brown JM (2014) Untangling the influences of unmodeled evolutionary processes on phylogenetic signal in a forensically important HIV-1 transmission cluster. Mol Phylogenet Evol., 75:126-137.