Resume

• 2009

  Scripps Outstanding Speakers (SOS)

  Advanced Communicator Bronze (ACB)

  Vice President of Education

  Secretary

  Toastmasters International

• 2007

  American Association for the Advancement of Science

• 2006

  Ph.D.

  Chemistry

  American Chemical Society

  American Association for the Advancement of Science

  Toastmasters International (Scripps Outstanding Speakers)

  The Scripps Research Institute

• 2003

  San Diego

  California

  Design and synthesis of antiviral (SARS

  HCV) small molecules

  Senior Associate Scientist

  Pfizer

  Greater San Diego Area

  Adjunct Faculty

  Point Loma Nazarene University

  Palomar College

  San Diego Miramar College

  San Diego

  California

  Adjunct Faculty

• 2002

  Participated in Congressional Visits Day in Washington

  D.C. on behalf of ACS\n\nVisited with Congressman Duncan Hunter on behalf of ACS

  American Chemical Society Legislative Action Network

  2016 Chair-Elect

  San Diego Local Section

  American Chemical Society

  Spanish

  Greek

  Ancient (to 1453)

  English

  Bristol-Myers Squibb Graduate Fellowship

  Bristol-Myers Squibb

  Speaker at BioNet Symposium

  BioNet Symposium

  San Diego

  California

  Amgen Graduate Research Fellowship

  Amgen

  “Nicotine vaccine could vanish cigarette habits in a puff of smoke”

  by Fiona Barry\nhttp://www.biopharma-reporter.com/Bio-Developments/Nicotine-vaccine-could-vanish-cigarette-habits-in-a-puff-of-smoke

  Biopharma-Reporter

  Guest for Radio Conversation

  Joined KPBS radio host Maureen Cavanaugh and fellow guest Dr. Tom Novotny for a conversation about nicotine vaccine research recently featured in Journal of Medicinal Chemistry.\nhttp://www.kpbs.org/news/2015/jan/12/scripps-scientists-discover-new-vaccine-help-smoke/

  KPBS Midday Edition

  Harold G. Snyder Undergraduate Summer Research Fellowship

  Department of Chemistry

  University of Illinois

  “The Future of Quitting: A Nicotine Vaccine”

  https://www.youtube.com/watch?v=jfbL8quK3a0

  ACS Headline Science

  International Paper Company Chemical Sciences Scholarship

  International Paper Company Foundation

  \"Dispute over the legal rights to an anticancer agent continues\"​

  by Stu Borman\nhttp://cen.acs.org/articles/95/i7/Dispute-over-legal-rights-anticancer.html

  Chemical & Engineering News

  “Fog Clearing On TIC10 Drug Development Mix-Up”

  News coverage of our cancer research by Stu Borman of C&EN\nhttp://cen.acs.org/articles/92/i23/Fog-Clearing-TIC10-Drug-Development.html

  Chemical & Engineering News

  “Structure Error-Caused-Cancer-Drug-Mix-Up”

  A top story of 2014 in C&EN\nhttp://2014.cenmag.org/structure-error-caused-cancer-drug-mix-up/

  Chemical & Engineering News

  “Scientist in the Spotlight: Vaccine Fights Nicotine Addiction”

  by Lily Barback\nhttp://digital.laboratoryequipment.com/labequipment/lab_outlook_march_2015#pg24

  LabOutlook

  “Scripps finds flaw in cancer drug patent”

  News coverage of our cancer research by Bradley Fikes of the U-T\nhttp://www.utsandiego.com/news/2014/may/22/cancer-drug-misidentified-Janda/

  San Diego Union-Tribune

  “Tug Of War Over Promising Cancer Drug Candidate”

  News coverage of our cancer research by Stu Borman of C&EN\nhttp://cen.acs.org/articles/92/web/2014/05/Tug-War-Over-Promising-Cancer.html

  Chemical & Engineering News

  First Annual TSRI Lightning Talks Competition Finalist (Top 12)

  TSRI Society of Fellows

• 2001

  Pfizer

  California Institute for Biomedical Research

  University of San Diego

  La Jolla

  Synthesis of inhibitors of tuberculosis

  fibrosis

  and osteoarthritis pain; exploration of formulation tactics for altering drug pharmacokinetics at injection site

  Postdoctoral Fellow

  California Institute for Biomedical Research

  Kalamazoo

  Michigan

  Linezolid analog design and synthesis

  Associate Scientist

  Pharmacia

  La Jolla

  California

  Meroterpenoid natural product synthesis

  Graduate Student

  The Scripps Research Institute

  San Diego

  CA

  Instructor for chemistry laboratory courses (CHEM 301L and 152L)

  Adjunct Assistant Professor

  University of San Diego

  La Jolla

  CA

  Nicotine

  heroin

  cocaine

  and methamphetamine vaccine development; synthesis of proneurogenic and proapoptotic small molecules

  Research Associate

  The Scripps Research Institute

• 1997

  B.S.

  Chemistry

  Undergraduate research in the Robert M. Coates group

  University of Illinois at Urbana-Champaign

  Modern Organic Synthesis

  Classics in Total Synthesis

  Heterocyclic Chemistry

  Bioorganic Chemistry

  Spectroscopy

• 877

  There are disclosed imidazolinopyrimidinone compounds that have activity to induce TRAIL gene expression in macrophages. There is further disclosed a method for treating various cancers comprising administering effective amounts of an imidazolinopyrimidinone having the structure of Formula I herein. The invention is directed

  in various embodiments

  to a compound and pharmaceutical composition comprising an effective amount of a compound capable of inducing expression of TRAIL gene in cells capable of expressing the TRAIL gene to produce the cytokine TRAIL.

  Pharmacophore For Trail Induction

  Nicholas Jacob

  Kim Janda

• 2

  The regioisomer ratios (3°

  2°/2°

  3°)

  and in some cases the stereochemistry

  of vicinal azidohydrins formed in reactions of 11 trisubstituted terpene epoxides with Et2AlN3 in toluene are reported. The more highly substituted azide usually predominated (3°

  2°/2°

  3° ratios ≥ 40:1 to 2.5−1) in accord with a Markovnikov orientation and an SN1-like transition state. Reversed regioisomer ratios were observed with 6

  7-epoxygeranyl acetate (1:2.5) and cis-1

  2-epoxylimonene (1:3.3 to 1:10). The tertiary azido diols from 2

  3-epoxygeraniol

  3-epoxyfarnesol

  and 2

  3-epoxynerol were formed as single isomers with inversion of configuration at C3 (≥ 35−40:1 for the C10 azido diols). The regioselectivity was affected by the presence and proximity of oxy functional groups on the epoxide substrate (OH

  OAc

  and OSi-tBuMe2)

  the equivalents of Et2AlN3

  and additives (EtOAc or EtOH). The results and trends are rationalized by consideration of the structural and stereoelectronic characteristics of proposed diethylaluminum epoxonium ion intermediates and transition states

  together with the nucleophilicity of the azide donor. Six of the 3°

  2° azidohydrins were converted to the corresponding aziridines by primary-selective silylations of four azido diols

  mesylations

  and reductive cyclizations with LiAlH4.

  Regio- and Stereoselectivity of Diethylaluminum Azide Opening of Trisubstituted Epoxides and Conversion of the 3° Azidohydrin Adducts to Isoprenoid Aziridines

  Kim Janda

  The immunopotentiator tucaresol was modified for incorporation into liposomes

  where it was found to be a superior adjuvant to MPLA for vaccination against methamphetamine.

  Lipid tucaresol as an adjuvant for methamphetamine vaccine development

  Phil S. Baran

  Qianghui Zhou

  Darryl D. Dixon

  A scalable

  divergent synthesis of bioactive meroterpenoids has been developed. A key component of this work is the invention of “borono-sclareolide”

  a terpenyl radical precursor that enables gram-scale preparation of (+)-chromazonarol. Subsequent synthetic operations on this key intermediate permit rapid access to a variety of related meroterpenoids

  many of which possess important biological activity.

  Scalable

  Divergent Synthesis of Meroterpenoids via “Borono-sclareolide”

  Phil S. Baran

  Rune Risgaard

  Darryl D. Dixon

  Practical radical cyclizations using organoboronic acids and trifluoroborates take place in water

  open to air

  and in a scalable fashion employing catalytic silver nitrate and stoichiometric potassium persulfate. Both Pschorr-type cyclizations and tandem radical cyclization/trap cascades are described

  illustrating the utility of these mild conditions for the generation of polycyclic scaffolds.

  Practical Radical Cyclizations with Arylboronic Acids and Trifluoroborates

  Adult neurogenesis in the dentate gyrus (DG) is strongly influenced by drug-taking behavior and may have a role in the etiology of drug-seeking behavior. However

  mechanistic studies on the relationship of neurogenesis on drug seeking are limited. Outbred Wistar rats experienced extended access methamphetamine self-administration and individual differences in drug taking defined animals with higher preferred and lower preferred levels of drug intake. Forced abstinence from higher preferred levels of drug taking enhanced neurogenesis and neuronal activation of granule cell neurons (GCNs) in the DG and produced compulsive-like drug reinstatement. Systemic treatment with the drug Isoxazole-9 (a synthetic small molecule known to modulate neurogenesis in the adult rodent brain) during abstinence blocked compulsive-like context-driven methamphetamine reinstatement. Isoxazole-9 modulated neurogenesis

  neuronal activation and structural plasticity of GCNs

  and expression of synaptic proteins associated with learning and memory in the DG. These findings identify a subset of newly born GCNs within the DG that could directly contribute to drug-seeking behavior. Taken together

  these results support a direct role for the importance of adult neurogenesis during abstinence in compulsive-like drug reinstatement.

  A synthetic small-molecule Isoxazole-9 protects against methamphetamine relapse

  Feng Wang

  Franzblau

  S. G.

  Yu

  C.

  Vilchèze

  C.

  Yano

  T.

  Liu

  R.

  Harbut

  M. B.

  The generation of ATP through oxidative phosphorylation is an essential metabolic function for Mycobaterium tuberculosis (Mtb)

  regardless of the growth environment. The type II NADH dehydrogenase (Ndh-2) is the conduit for electrons into the pathway

  and is absent in the mammalian\ngenome

  thus making it a potential drug target. Herein

  we report the identification of two types of small molecules as selective inhibitors for Ndh-2 through a multicomponent highthroughput screen. Both compounds block ATP synthesis

  lead to effects consistent with loss of NADH turnover

  and\nimportantly

  exert bactericidal activity against Mtb. Extensive medicinal chemistry optimization afforded the best analogue with an MIC of 90 nM against Mtb. Moreover

  the two scaffolds have differential inhibitory activities against the two homologous Ndh-2 enzymes in Mtb

  which will allow precise control over Ndh-2 function in Mtb to facilitate the assessment of this anti-TB drug target.

  Small Molecules Targeting Mycobacterium tuberculosis Type II NADH Dehydrogenase Exhibit Antimycobacterial Activity

  Kim D. Janda

  Vladimir V. Kravchenko

  Nicholas T. Jacob

  Angewandte Chemie International Edition

  Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an immunosurveillance cytokine that kills cancer cells but demonstrates little toxicity against normal cells. While investigating the TRAIL-inducing imidazolinopyrimidinone TIC10

  a misassignment of its active structure was uncovered. Syntheses of the two isomers

  corresponding to the published and reassigned structures

  are reported. The ability of each to induce TRAIL expression in macrophages was investigated and it was found that only the compound corresponding to the reassigned structure shows the originally reported activity; the compound corresponding to the published structure is inactive. Importantly

  this structural reassignment has furnished a previously unknown antitumor pharmacophore.

  Pharmacophore Reassignment for Induction of the Immunosurveillance Cytokine TRAIL

  Kim D. Janda

  Gary Fujii

  Thai Q. Do

  A major liability of existing nicotine vaccine candidates is the wide variation in anti-nicotine immune responses among clinical trial participants. In order to address this liability

  significant emphasis has been directed at evaluating adjuvants and delivery systems that confer more robust potentiation of the anti-nicotine immune response. Toward that end

  we have initiated work that seeks to exploit the adjuvant effect of liposomes

  with or without Toll-like receptor agonist(s). The results of the murine immunization study described herein support the hypothesis that a liposomal nicotine vaccine formulation may provide a means for addressing the immunogenicity challenge.

  Enhancing nicotine vaccine immunogenicity with liposomes

  Jonathan

  Lockner

  San Diego Miramar College

  Palomar College

  Point Loma Nazarene University

  The Scripps Research Institute

• Kalamazoo Christian High School

  Chair

  American Chemical Society

  San Diego Local Section

  NMR spectroscopy

  Peptide Synthesis

  Synthetic Organic Chemistry

  Organometallic Chemistry

  Organic Synthesis

  Small Molecules

  HPLC

  Organic Chemistry

  SciFinder

  NMR

  Lead Change

  Drug Design

  Drug Discovery

  LC-MS

  Purification

  Chemical Biology

  Mass Spectrometry

  Natural Products

  Medicinal Chemistry

  Chemistry

  Flagellin as Carrier and Adjuvant in Cocaine Vaccine Development

  Kim Janda

  Ian Wilson

  Robin Rosenfeld-Gunn

  Joel Schlosburg

  Jennifer Choi

  Lisa Eubanks

  Cocaine abuse is problematic

  directly and indirectly impacting the lives of millions

  and yet existing therapies are inadequate and usually ineffective. A cocaine vaccine would be a promising alternative therapeutic option

  but efficacy is hampered by variable production of anti-cocaine antibodies. Thus

  new tactics and strategies for boosting cocaine vaccine immunogenicity must be explored. Flagellin is a bacterial protein that stimulates the innate immune response via binding to extracellular Toll-like receptor 5 (TLR5) and also via interaction with intracellular NOD-like receptor C4 (NLRC4)

  leading to production of pro-inflammatory cytokines. Reasoning that flagellin could serve as both carrier and adjuvant

  we modified recombinant flagellin protein to display a cocaine hapten termed GNE. The resulting conjugates exhibited dose-dependent stimulation of anti-GNE antibody production. Moreover

  when adjuvanted with alum

  but not with liposomal MPLA

  GNE-FliC was found to be better than our benchmark GNE-KLH. This work represents a new avenue for exploration in the use of hapten-flagellin conjugates to elicit anti-hapten immune responses.

  Flagellin as Carrier and Adjuvant in Cocaine Vaccine Development

  Kim D. Janda

  Janaina Vendruscolo

  A leading nicotine conjugate vaccine was only efficacious for one-third of clinical trial participants

  likely due in part to its use of racemic nicotine hapten

  (±)-3′-AmNic. Immunization of male Wistar rats with (+)-

  (−)-

  or (±)-3′-AmNicSucTT and subsequent antibody immunoassays suggest that a vaccine using enantiopure (−)-3′-AmNic hapten imparts superior capacity to bind (−)-nicotine. Future nicotine vaccine clinical candidates must incorporate this design consideration (i.e.

  hapten enantiopurity) in order to maximize efficacy.

  A Conjugate Vaccine Using Enantiopure Hapten Imparts Superior Nicotine-Binding Capacity

  Kim Janda

  The worldwide prevalence of nicotine addiction

  the dramatic extent to which this addiction negatively impacts human health

  and the huge economic burden it creates for health care

  demand that interventive support for this condition continue to be developed. Immunopharmacotherapy is a type of interventive tactic that has been examined for a variety of addictive and toxic small molecules

  including nicotine. Essentially

  an immunogen is designed in order that the elicited antibody response will be directed at generating anti-nicotine antibodies

  which are able to bind nicotine in the bloodstream

  reduce its concentration in the brain

  and thus de-incentivize the further use of nicotine products. This cessation aid is complementary to pharmaceutical and psychosocial therapies

  and

  when used in conjunction with these other tactics

  would dramatically impact the likelihood that smokers who are motivated to quit would successfully achieve that end. Much work has been done over the past twenty years in the area of nicotine vaccine research

  and

  while proof-of-principle has been demonstrated

  further efforts in vaccine design

  particularly adjuvant science

  must be made toward developing a broadly efficacious nicotine vaccine. This chapter is intended to provide a retrospective view of developments in the field

  highlight specific opportunities for future research investment

  and ultimately make the case that

  despite the challenges and pitfalls that have marked this path

  the journey toward a successful marketed nicotine vaccine for smoking cessation must continue.

  Immunopharmacotherapy for Nicotine Addiction (book chapter)

  George F. Koob

  Kim D. Janda

  Scott Edwards

  G. Neil Stowe

  Ashlee A. K. Nunes

  Carrie L. Wade

  Leandro F. Vendruscolo

  Joel E. Schlosburg

  Heroin addiction

  a chronic relapsing disorder characterized by excessive drug taking and seeking

  requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream

  preventing entry into the brain and nullifying psychoactivity. However

  this strategy is complicated by heroin’s rapid metabolism to 6-acetylmorphine and morphine. We recently developed a “dynamic” vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin’s metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats

  preventing various features of drugs of abuse: heroin reward

  drug-induced reinstatement of drug seeking

  and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin

  even in subjects with a history of dependence. In addition

  targeting a less brain-permeable downstream metabolite

  morphine

  is insufficient to prevent heroin-induced activity in these models

  suggesting that heroin and 6-acetylmorphine are critical players in heroin’s psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics

  it can be used in conjunction with available treatment options. Thus

  our vaccine represents a promising adjunct therapy for heroin addiction

  providing continuous heroin antagonism

  requiring minimal medical monitoring and patient compliance.

  Dynamic vaccine blocks relapse to compulsive intake of heroin

  Kim D. Janda

  Lisa M. Eubanks

  Nicholas T. Jacob

  Despite efforts to produce suitable smoking cessation aids

  addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has been to elicit a sufficiently high antibody concentration to curb nicotine distribution to the brain. Herein

  we detail investigations into a new hapten design

  which was able to elicit an antibody response of significantly higher specificity for nicotine. We also explore the use of a mutant flagellin carrier protein with adjuvanting properties. These studies underlie the feasibility of improvement in antinicotine vaccine formulations to move toward clinical efficacy.

  Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development

  Robert M. Coates

  Jessica L. Bailey

  Chad E. Davis