JOHN BAXTER BIGGINS, Ph.D.

PROFESSIONAL EXPERIENCE:

2022-Present: Mount Sinai South Nassau; Senior Research Director – Neurology/Neurosurgery

2016-2021: LifeMine Therapeutics; Senior Scientist, Data Sciences – Target Evaluation (2021); Genomics (2019-2020); Scientist II, Natural Products Biosynthesis (2017-2019); Scientific consultant (2016).

2016-Present: LifeMine Therapeutics; Senior Scientist, Data Sciences – Target Evaluation (2021- Present); Genomics (2019-2020); Scientist II, Natural Products Biosynthesis (2017-2019); Scientific consultant (2016).

Founding team member – directly responsible for the development of a novel drug discovery platform, wherein specific genetic codes in microbial genomes were identified that reliably predict the pharmacological target of bioactive small molecules, thus bypassing traditional labor-intensive fermentation techniques. Genomic data from thousands of sequenced microbial genomes reliably provided for the discovery of bespoke drug candidates, from which multiple clinically relevant drug candidates were determined in silico and later biochemically confirmed. The intellectual property of this platform has to-date secured >$100 million in venture capital funding.

2016: Hofstra University; Department of Chemistry. Special Assistant Professor.
Instructor at-large for undergraduate chemistry lecture and laboratory courses, with additional student mentoring duties.

2009-2016: The Rockefeller University; Laboratory of Genetically Encoded Small Molecules. Senior
Scientist (2014-2016); Postdoctoral Fellow (2009-2014). Advisor: Sean F. Brady, Ph.D.
The influences that microbial secondary metabolism (small molecule biosynthesis) has on bacterial virulence was assessed through a systematic chemical biology approach. Using CDC Priority
Pathogen-class Burkholderia species as a model, small molecule virulence factors, primarily peptide and polykide-based, encoded within bacterial genomes were bioinformatically identified, had their
biosyntheses induced, were purified, and were structurally characterized. The putative roles that these small molecules have in pathogenicity were then confirmed through both in vitro and in vivo
models. In addition, an industrial-scale survey of worldwide soil-derived metagenomes was conducted for mining potential bioactive small molecules for next-generation therapeutics.

2004-2008: University of Delaware; Department of Chemistry and Biochemistry (2003-2008). Robert Black-Damon Runyon Postdoctoral Fellow. Advisor: John T. Koh, Ph.D.
Determinates of the proteins involved in neuron axon guidance and plasticity were explored in a spatially- and temporally-focused manner, whereby targeted gene expression lays under the control of a photo-caged hormonal activation system. Additionally, a novel chemogenetic approach towards mapping nuclear/non-nuclear cross talk among nuclear hormone receptor signaling pathways was initiated.

1997-2003: University of Wisconsin-Madison; School of Pharmacy (2001-2003); Memorial Sloan- Kettering Cancer Center; Molecular Pharmacology and Chemistry (1997-2001); Laboratory for
Biosynthetic Chemistry. PhRMA Foundation and Frank Lappin Horsfall, Jr. Predoctoral Fellow. Advisor: Jon S. Thorson, Ph.D.
In exploring enediyne antibiotic biosynthesis and self-resistance, a self-sacrificing radical-quenching self-resistance protein (CalC) within the calicheamicin producing Micromonospora bacterium was
discovered and physically characterized along with the development of a hyper-sensitive real-time DNA cleavage assay. In addition, an efficient method for in vitro chemoenzymatic synthesis of
nucleotide sugars was developed via a sugar nucleotidyltransferase enzyme, engineered to accept a wide range of unnatural substrates towards the glycorandomization of bioactive molecules.

1995-1997: Fordham University; Department of Chemistry. Laboratory Technician.
Instructed undergraduates within an organic chemistry laboratory course and three additional chemistry (Food, Forensic, and Art) courses. Provided maintenance and technical support to the Dept. of Chemistry at-large. Optimized a Grignard-based synthetic scheme suitable for an undergraduate curriculum. Biggins – Curriculum Vitae 2

1993-1994: Fordham University; Department of Chemistry. Undergraduate Research Assistant. Advisor: James Ciaccio, Ph.D.
Initiated the development of a Grignard-based synthetic scheme suitable for an undergraduate curriculum.

1993: New York Hospital-Cornell Medical Center (Westchester Division). Summer Research Intern. Advisor: Danielle Greenberg, Ph.D.
Determining the satiating behavioral effects of sham and real feeding upon rats exposed to lipid-based dietary stimuli.

EDUCATION: Cornell University and Sloan-Kettering Institute
Weill Graduate School of Medical Sciences, New York, NY 2004: Ph.D., Pharmacology

Thesis: “The Mechanism of CalC: a Protein Conferring Self-Resistance to the Antitumor Antibiotic Calicheamicin within Micromonospora echinospora ssp. calichensis.” Fordham University, Bronx, NY
1994: B.S., Chemistry 1993: B.S., Psychology

TECHNICAL SKILLS:

Academic

• Extensive training in chemical biology, synthetic biology, biochemistry, organic chemistry, genetics, and molecular biology with emphasis on oncologic, infectious, and metabolic diseases.
• Successful grant-writing experience (Private grants/awards, NIH R01/U01 project grants).
• Teaching/mentoring experience in college/professional level classroom and laboratory settings Scientific
• Organic/analytical chemistry benchwork
• Molecular biology benchwork
• 2D-NMR
• X-ray crystallography
• Bioinformatics modeling
• Next-generation sequencing (Ion Torrent, HiSeq)
• HPLC/GC
• FT-IR
• High throughput screening instrumentation
• Flow cytometry
• FPLC/protein purification (IEX, SEC)
• Proteomic analysis (CD, Fluorescence)
• Gene array
• PCR/qPCR
• Mass spectrometry (MALDI, ESI, MS/MS)

AWARDS AND HONORS:
2005-2008: Damon Runyon Cancer Research Foundation: Robert Black Fellowship Award
2005: PhRMA Foundation: Postdoctoral Fellowship in Pharmacology/Toxicology (personally declined for Damon Runyon fellowship)
2004: Cornell University, Weill Medical College: Julian R. Rachele Research Prize
2003: Gordon Research Conference; Bioorganic Chemistry: Pfizer Prize
2001-2002: Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation; Fellowship for Advanced Predoctoral Training in Pharmacology and Toxicology
2001: Cornell University; Vincent duVigneaud Memorial Symposium: Vincent duVigneaud Prize Memorial Sloan-Kettering Cancer Center; Frank Lappin Horsfall, Jr. Fellowship
2000: Cornell University; Vincent duVigneaud Memorial Symposium: Vincent duVigneaud Prize
1993: New York Hospital-Cornell Medical Center (Westchester Div.); Bourne Behavioral Research Laboratory, Summer Research Intern
1992-1993: Fordham University; Honors Program in Psychology

PATENTS:
2. Submitted (2018).
Biggins – Curriculum Vitae 3
1. Biggins, J.B., Bowman, B.R., and Verdine, G.L. (2017) Human therapeutic targets and modulators
thereof. WO2019055816A1

PUBLICATIONS:
24. Peek, J. Lilic, M., Montiel, D., Milshteyn, A., Woodworth, I., Biggins, J.B., Ternei, M.A., Calle, P.Y.,
Danziger, M., Warrier, T., Saito, K., Braffman, N., Fay, A., Glickman, MS., Darst, S.A., Campbell, E.A.,
and Brady, S.F. (2018). “Rifamycin congeners kanglemycins are active against rifampicinresistant bacteria via a distinct mechanism.” Nat. Commun. 9(1):4147.
23. Xu, L., Biggins, J.B., Bowman, B.R., Verdine, G.L., Gloer, J.B., Alspaugh, J.A., and Bills, G.F. (2018)
“Identification of cyclosporin C from Amphichorda felina using a Cryptococcus neoformans differential temperature sensitivity assay.” Appl. Microbiol. Biotechnol. 102(5):2337-2350.
22. Marnix, M.H, Kottmann, R., Yilmaz, P., Cummings, M, Biggins, J.B., et al. (2015) “The Minimum Information about a Biosynthetic Gene cluster (MIBiG) specification.” Nature Chem Biol. 11:625.
21. Biggins, J.B., Kang, H-S., Ternei, M.A., DeShazer, D., and Brady, S.F. (2014) “The Chemical Arsenal of Burkholderia pseudomallei is Essential for Pathogenicity.” J. Amer. Chem. Soc. 136(26):9484-9490.
20. Biggins, J.B., Ternei, M. and Brady, S.F. (2012) “Malleilactone, a Polyketide Synthase-Derived Virulence Factor Encoded by the Cryptic Secondary Metabolome of Burkholderia pseudomallei Group
Pathogens.” J. Amer. Chem. Soc. 134(32):13192-13195.
19. Biggins, J.B., Gleber, C.D., and Brady, S.F. (2011) “Acyldepsipeptide HDAC Inhibitor Production Induced in Burkholderia thailandensis.” Org. Lett. 13(6):1536-1539.
18. Biggins, J.B., Liu, X., Feng, Z., and Brady, S.F. (2010) “Metabolites from the Induced Expression of Cryptic Single Operons Found in the Genome of Burkholderia pseudomallei.” J. Amer. Chem. Soc.
133:1638-1641.
17. Sauers, D, Temburni, M.K., Biggins, J.B., Galileo, D., and Koh, J.T. (2010) “Light Directed Gene Patterning With Soluble Effectors: Differential Protein Expression Directs Cell Segregation.” ACS Chem.
Biol. 5(3):313-320.
16. Biggins, J.B., Hashimoto, A., and Koh, J.T. (2007) “Photo-Caged Agonist for Analog-Specific form of the Vitamin D Receptor.” ChemBioChem. 8(7):799-803.
15. Biggins, J.B. and Koh, J.T. (2007) “Chemical Biology of Steroid and Nuclear Hormone Receptors.”
Curr. Opin. Chem. Biol. 11:99-110.
14. Biggins, J.B., Prudent, J.R., Marshall, D.J., and Thorson, J.S. (2006) “A Continuous Assay for DNA Cleavage Using ‘Molecular Break Lights’.” Methods. Mol. Biol. 335:83-92.
13. Koh, J.T. and Biggins, J.B. (2005) “Ligand Receptor Engineering and its Applications towards the Complementation of Genetic Diseases and Target Identification.” Curr. Top. Med. Chem. 5(4):413-420.
12. Biggins, J.B., Onwueme, K.C., and Thorson, J.S. (2003) “Resistance to Enediyne Antitumor Antibiotics by CalC Self-Sacrifice.” Science. 301(3659): 1537-1541. (Highlights in Chemical & Engineering News;
Sept. 15, 2003, p. 4., Nat. Rev. Microbiol. Nov. 2003, v. 1(2), p. 88, and The Scientist (daily news); Sept. 12, 2003.)
11. Yang, J., Fu, X., Jia, Q., Shen, J., Biggins, J.B., Jiang, J., Zhao, J., Schmidt, J. J., Wang, P. G., and Thorson, J. S. (2003) “Studies on the Substrate Specificity of E. coli Galactokinase.” Org. Lett.
5(13):2223-2226.
10. Albermann, C., Soriano, A., Jiang, J., Vollmer, H., Biggins, J.B., Barton, W.A., Lesniak, J., Nikolov, D.B., and Thorson, J.S. (2003) “Substrate Specificity of NovM: Implications for Novobiocin
Biosynthesis and Glycorandomization.” Org. Lett. 5(6):933-936.
9. Losey, H., Jiang, J., Biggins, J.B., Oberthur, M., Ye, X-Y., Dong, S.D., Kahne, D., Thorson, J.S., and Walsh, C.T. (2002) “Incorporation of Glucose Analogs by Glycosyltransferases GtfE and GtfD from the Vancomycin Biosynthetic Pathway to Generate Variant Glycopeptides.” Chem. Biol. 9:1305-1314.
8. Barton, W.A., Biggins, J.B., Jiang, J., Thorson, J.S., and Nikolov, D.B. (2002) “Expanding Pyrimidine
Diphosphosugar Libraries via Structure-Based Nucleotidyltransferase Engineering.” Proc. Nat. Acad.
Sci. USA. 99(21):13397-13402.
Biggins – Curriculum Vitae 4
7. Barton, W.A., Lesniak, J., Biggins, J.B., Jeffrey, P.D., Jiang, J., Rajashankar, K.R., Thorson, J.S., and
Nikolov, D.B. (2001) “Structure, Mechanism, and Engineering of a Nucleotidyltransferase as a First Step
Toward Glycorandomization.” Nat. Struct. Biol. 8(6):545-551. (Highlights in Chemical & Engineering News; June 4, 2001, p. 11 & Dec. 10, 2001, p. 50.)
6. Jiang, J., Biggins, J.B., and Thorson, J.S. (2001) “Expanding the Pyrimidine Diphosphosugar Repertoire: The Chemoenzymatic Synthesis of Amino- and Acetamidoglucopyranosyl Derivatives.”
Angew. Chem. Int. Ed. 40(8):1502-1505.
5. Thorson, J.S., Hosted, T.J. Jr., Jiang, J., Biggins, J.B., Ahlert, J., and Ruppen, M. (2001) “Nature’s Carbohydrate Chemists: The Enzymatic Glycosylation of Bioactive Bacterial Metabolites.” Curr. Org.
Chem. 5:139-167.
4. Ciaccio, J.A., Bravo, R.P., Drahus, A.L., Biggins, J.B., Concepcion, R.A., and Cabera, D. (2001)
“Diastereoselective Synthesis of (+/-)-1,2-Diphenyl-1,2-propanediol: A Discovery-Based Grignard Reaction Suitable for a Large Organic Lab Course.” J. Chem. Ed. 78:531.
3. Biggins, J.B., Prudent, J.R., Marshall, D.J., Ruppen, M., and Thorson, J.S. (2000) “A Continuous Assay for DNA Cleavage: The Application of “Break Lights” to Enediynes, Iron-Dependent Agents, and Nucleases.” Proc. Nat. Acad. Sci. USA. 97(25):13537-13542. (Highlight in Chemical & Engineering
News; Dec. 11, 2000, pp. 51-52.)
2. Jiang, J.*, Biggins, J.B.*, and Thorson, J.S. (2000) “A General Enzymatic Method for the Synthesis of Natural and ‘Unnatural’ UDP- and TDP-Nucleotide Sugars.” J. Am. Chem. Soc. 122(28):6803-6804.
1. Zhao, Y, Biggins, J.B., and Thorson, J.S. (1998) “Acceptor Specificity of Salmonella GDPMan: aLRha1à3aDGal-PP-Und-􀀀1à4-Mannosyltransferase: A Simplified Assay Based on Unnatural
Acceptors.” J. Am. Chem. Soc. 120(49):12986-12987.

INVITED SEMINARS:
LifeMine Therapeutics; Oct, 13, 2016
ContraFect; Jan. 22, 2016
Pfizer; Worldwide Medicinal Chemistry, Oct. 7, 2014
John Jay College of Criminal Justice; Department of Sciences, Feb. 10, 2014
Northeast Biodefense Center; Annual Conference, Columbia University. Nov. 2, 2009
GlycoFi; October 10, 2008
Damon Runyon Cancer Research Foundation; Fellows Retreat. Oct. 8. 2007
Dade Behring; July 12, 2007
Fordham University; Dept. of Chemistry. Nov. 15, 2006

COMPETITIVE FELLOWSHIPS/SUPPORT
Drug Discovery Platform Grant Jan 2014 – Jan 2015
Robertson Therapeutic Development Fund
“New Drugs for Melioidosis.”
$45,000
Postdoctoral Fellowship Jan 2005 – Dec 2007
Damon Runyon Cancer Research Foundation
“A chemogenetic approach towards elucidating non-genomic nuclear hormone receptor signaling.”
Fellowship Award (DRG 1852-05); supported by the Robert Black Charitable Foundation.
$134,000
Predoctoral Fellowship Jan 2001 – Dec 2002
Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation
“Mechanism of self-resistance in Micromonospora to the antitumor antibiotic calicheamicin.”
Advanced Predoctoral Training in Pharmacology and Toxicology
$25,000
Predoctoral Fellowship May 2001
Memorial Sloan-Kettering Cancer Center
Frank Lappin Horsfall, Jr. Fellowship
Awarded for publication of: Biggins et. al (2000) Proc. Nat. Acad. Sci. USA. 97(25):13537-13542.
$8,000
Biggins – Curriculum Vitae 5

RELEVANT EXPERIENCE:
Cornell University, Cornell Institute for Biology Teachers; Ithaca, NY
•CIBT Summer Program in Molecular Biology. Mentor and lecture New York State tenured high school
Biology teachers in the advancements in molecular 1biology in efforts to provide increased practical
knowledge with which to innovate and instruct a high school biology/chemistry laboratory course.
Weill Graduate School of Medical Sciences; New York, NY
•Cornell Science Challenge. Mentor elementary school students in developing, preparing, and carrying
out a protocol for scientific exploration.
Acedemic courses taught:
• Introductory Chemistry
• Introductory Chemistry I Lab
• Introductory Chemistry II Lab
• Organic Chemistry I Lab
• Organic Chemistry II Lab
• Forensic Chemistry I Lab
• Food Chemistry Lab
• Chemistry of Art Lab