RANDALL THEODORE PETERSON portrait
  • L. S. Skaggs Presidential Endowed Chair and Dean, College Of Pharmacy
  • Professor, Pharmacology And Toxicology
801-587-3064

Presentations

  • My scientific journey to the University of Utah graduate student recruiting event . Invited Talk/Keynote, Presented, 01/2023.
  • My scientific journey to the University of Utah graduate student recruiting event. Invited Talk/Keynote, Presented, 01/2022.
  • Bringing new medicines to life Osher center for lifelong learning . Invited Talk/Keynote, Presented, 01/2022.
  • Bringing new medicines to life Education Resource Development Council. Invited Talk/Keynote, Presented, 01/2022.
  • Scaling up: gene and therapy discovery using scalable in vivo technologies Center for Genomic Medicine annual retreat . Invited Talk/Keynote, Presented, 01/2022.
  • Scaling up: zebrafish screening for pain genes and drugs? University of Utah Pain Workshop . Invited Talk/Keynote, Presented, 01/2022.
  • My scientific journey to the University of Utah graduate student recruiting event. Invited Talk/Keynote, Presented, 01/2021.
  • My scientific journey to the University of Utah graduate student recruiting event. Invited Talk/Keynote, Presented, 01/2020.
  • High-throughput biology at the organismal level The Svedberg lecture, Uppsala University, Sweden . Invited Talk/Keynote, Presented, 01/2023.
  • Scaling up: zebrafish accelerate cardiovascular drug and gene discovery Beth Israel Deaconess Medical Center seminar . Invited Talk/Keynote, Presented, 01/2022.
  • Scaling up: zebrafish accelerate drug and gene discovery Uppsala University seminar (virtual) . Invited Talk/Keynote, Presented, 01/2022.
  • New tools for light-mediated control of TRP channels Biophysical Society meeting – virtual . Invited Talk/Keynote, Presented, 01/2022.
  • Chemo-optogenetic probes for light-controlled switching of ion channels 20th IUPAB Congress, 45th Annual SBBf Meeting, and 50th Annual SBBq Meeting . Invited Talk/Keynote, Presented, 01/2021.
  • Scaling up: phenotypic screens in zebrafish identify new drugs and drug toxicities United States Food and Drug Administration (FDA) . Invited Talk/Keynote, Presented, 01/2021.
  • Scaling up: zebrafish social interaction as scalable phenotype for identifying neurodevelopmental toxicants and their mechanisms Society for Birth Defects Research & Prevention annual meeting – virtual . Invited Talk/Keynote, Presented, 01/2021.
  • Zebrafish in chemical biology and drug discovery(and crispr screens!) University of Sao Paulo – virtual due to pandemic . Invited Talk/Keynote, Presented, 01/2021.
  • MIC-Drop: A platform for large-scale CRISPR screens Zebrafish Disease Models Society annual meeting – virtual due to pandemic . Invited Talk/Keynote, Presented, 01/2021.
  • Scaling up: Zebrafish behaviors as scalable phenotypes for small molecule screening American Chemical Society annual meeting - virtual . Invited Talk/Keynote, Presented, 01/2021.
  • Can zebrafish screens really lead to new human medicines? International Zebrafish Society monthly webinar . Invited Talk/Keynote, Presented, 01/2020.
  • Zebrafish behaviors as scalable, high-content readouts of genetic and chemical perturbations of brain function. NIMH Genes to Biology Virtual Workshop. Invited Talk/Keynote, Presented, 01/2020.
  • Chemo-optogenetic probes for light-controlled switching of Ion Channels International symposium in honor of Jindrich Kopecek, Salt Lake City, UT . Invited Talk/Keynote, Presented, 01/2020.

Grants, Contracts & Research Gifts

  • Chemical modifiers of complex genetic phenotypes. PI: Peterson RT. Novartis, 01/2003 - 01/2005. Total project budget to date: $643,000.00
  • Chemical genetic modifiers of acute myelogenous leukemia. PI: Peterson RT. NIH-NCI, 01/2006 - 01/2008. Total project budget to date: $525,000.00
  • Chemical tools for dissection of blood vessel identity. PI: Peterson RT. NIH – NHLBI, 01/2005 - 01/2009. Total project budget to date: $900,000.00
  • High-throughput behavioral screening for in vivo discovery of neuroactive drugs. PI: Peterson RT. NIH-NIMH, 01/2009 - 01/2011. Total project budget to date: $275,000.00
  • Rapid development of in vivo models for countermeasure discovery: organophosphate. PI: Peterson RT. NIH-NINDS, 01/2008 - 01/2012. Total project budget to date: $921,000.00
  • Discovery of novel cyanide countermeasures by high-throughput in vivo screening. PI: Peterson RT. US Army, 01/2007 - 01/2013. Total project budget to date: $671,000.00
  • In vivo discovery of psychotropic drugs by high-throughput behavioral phenotyping. PI: Peterson RT. NIH-NIMH, 01/2009 - 01/2013. Total project budget to date: $800,000.00
  • In vivo chemical biology of heart failure. PI: Peterson RT. American Heart Association, 01/2013 - 01/2015. Total project budget to date: $150,000.00
  • Ned Sahin Research Fund for Restoring Developmental Plasticity . PI: Peterson RT. Philanthropy, 01/2001 - 01/2016. Total project budget to date: $500,000.00
  • The Charles and Ann Sanders MGH Research Scholar Award. PI: Peterson RT. MGH, 01/2011 - 01/2016. Total project budget to date: $500,000.00
  • Models of schizophrenia and autism. PI: Peterson RT. Hoffmann-La Roche, 01/2013 - 01/2016. Total project budget to date: $888,000.00
  • Small molecule approach for inducing sterility in aquaculture. PI: Peterson RT. USDA, 01/2014 - 01/2016. Total project budget to date: $310,000.00
  • Optimizing novel cyanide countermeasures. PI: Peterson RT. NIH-NINDS, 01/2012 - 01/2017. Total project budget to date: $3,038,187.00
  • Training and education core. PI: Peterson RT. NIH-NINDS, 01/2012 - 01/2017. Total project budget to date: $1,202,362.00
  • A Platform for Identifying Drugs Targeting Germ Cells. PI: Peterson RT. Bill & Melinda Gates Foundation , 01/2017 - 01/2018. Total project budget to date: $100,000.00
  • Heart Failure Modeling & Small Molecule Screening. PI: Peterson RT. Merck & Company Inc., 01/2015 - 01/2019. Total project budget to date: $224,744.00
  • Targeted approach for mitochondrial disease treatments. PI: Peterson RT. Margolis Foundation , 01/2019 - 01/2020. Total project budget to date: $75,000.00
  • Advancing novel cyanide countermeasures. PI: Peterson RT. NIH-NINDS, 01/2019 - 01/2024. Total project budget to date: $16,000,000.00
  • Advancing gene-editing nucleases for diverse zebrafish applications. PI: Peterson RT. NIH-NIGMS, 01/2019 - 01/2023. Total project budget to date: $1,952,000.00

Research Interests

Developmental Biology: Small molecules are powerful tools for studying developmental biology because they provide timing and dosage control over developmental pathways that is difficult to achieve with genetic mutations. Unfortunately, only a handful of developmental pathways can currently be targeted with small molecules. We are discovering novel chemical modifiers of developmental pathways by exposing zebrafish embryos to libraries of structurally diverse small molecules and identifying those that induce specific developmental defects. Using screens of this type, we have discovered dozens of compounds that cause specific defects in hematopoesis, cardiac physiology, embryonic patterning, pigmentation, and morphogenesis of the heart, brain, ear, and eye and germ cell lineage.

Disease Physiology: One focus of our group is modeling human diseases in zebrafish. We then use the models to screen large chemical libraries for small molecule modulators of the disease-related phenotypes. The compounds we discover help us elucidate disease mechanisms and serve as starting points for developing new drug candidates.

Disease physiology is often complex and involves interactions between multiple organs and tissue types. Consequently, many diseases cannot be studied effectively using in vitro assays. The zebrafish is an excellent vertebrate model system to study many complexes, non-cell autonomous diseases because the diseases can be studied in a native, whole organism setting. In addition, compounds discovered in zebrafish screens have the advantage of having been selected for their ability to be active, efficacious, and well tolerated in animals.

Neuroscience & Behavior: Behaviors are accessible readouts of the molecular pathways that control neuronal signaling. Our group develops tools and techniques for comprehensive and high-throughput behavioral phenotyping in the zebrafish. These tools have some potential to improve our understanding of the neuronal signaling and may accelerate the pace of neuroactive drug discovery.

Zebrafish Reverse Genetics: Zebrafish have proven to be a powerful genetic tool over the years, primarily through forward genetic screens where fish are mutagenized (typically with chemical agent) and screened for obvious defects. We are now on the verge of the next exciting step in zebrafish genetics: reverse genetics! Using targeted DNA disruption, we are now making designer mutations in specific genes of interest. Here are some of the resent papers describing three different processes.

Publications

  • Nath AK & Ma J, Chen ZZ, Li Z, Vitery MDC, Kelley ML, Peterson RT, Gerszten RE, Yeh JJ (2020). Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish. FASEB J. Published, 01/2020.
  • Lam PY & , Kutchukian P, Anand R, Imbriglio J, Andrews C, Padilla H, Vohra A, Lane S, Parker DL Jr, Cornella Taracido I, Johns DG, Beerens M, MacRae CA, Caldwell JP, Sorota S, Asnani A, Peterson RT (2020). Cyp1 Inhibition Prevents Doxorubicin-Induced Cardiomyopathy in a Zebrafish Heart-Failure Model. Chembiochem. Published, 01/2020.
  • Tu J & Svatunek D, Parvez S, Eckvahl HJ, Xu M, Peterson RT, Houk KN, Franzini RM (2019). Isonitrile-responsive and bioorthogonally removable tetrazine protecting groups. Chem Sci. Published, 01/2019.
  • Torres JP & Lin Z, Fenton DS, Leavitt LU, Niu C, Lam PY, Robes JM, Peterson RT, Concepcion GP, Haygood MG, Olivera BM, Schmidt EW (2020). Boholamide A, an APD-Class, Hypoxia-Selective Cyclodepsipeptide. J Nat Prod. Published, 01/2020.
  • Weeks O & Bossé GD, Oderberg IM, Akle S, Houvras Y, Wrighton PJ, LaBella K, Iversen I, Tavakoli S, Adatto I, Schwartz A, Kloosterman D, Tsomides A, Charness ME, Peterson RT, Steinhauser ML, Fazeli PK, Goessling W (2020). Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood. J Clin Invest. Published, 01/2020.
  • Amgalan D, Garner TP, Pekson R, Jia XF, Yanamandala M, Paulino V, Liang FG, Corbalan JJ, Lee J, Chen Y, Karagiannis GS, Sanchez LR, Liang H, Narayanagari SR, Mitchell K, Lopez A, Margulets V, Scarlata M, Santulli G, Asnani A, Peterson RT, Hazan RB, Condeelis JS & Oktay MH, Steidl U, Kirshenbaum LA, Gavathiotis E, Kitsis RN (2020). A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy. Nat Cancer. Published, 01/2020.
  • Goldshtein H & Muhire A, Petel Légaré V, Pushett A, Rotkopf R, Shefner JM, Peterson RT, Armstrong GAB, Russek-Blum N (2020). Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis. Ann Clin Transl Neurol. Published, 01/2020.
  • Lam PY & Thawani AR, Balderas E, White AJP, Chaudhuri D, Fuchter MJ, Peterson RT. (2020). TRPswitch-A Step-Function Chemo-optogenetic Ligand for the Vertebrate TRPA1 Channel. J Am Chem Soc. Published, 01/2020.
  • Wu G & Dentinger BTM, Nielson JR, Peterson RT, Winter JM. (2021). Emerimicins V-X, 15-Residue Peptaibols Discovered from an Acremonium sp. through Integrated Genomic and Chemical Approaches. J Nat Prod. Published, 01/2021.
  • Bosse GD & Urcino C, Watkins M, Flórez Salcedo P, Kozel S, Chase K, Cabang A, Espino SS, Safavi-Hemami H, Raghuraman S, Olivera BM, Peterson RT, Gajewiak J. (2021). Discovery of a Potent Conorfamide from Conus episcopatus Using a Novel Zebrafish Larvae Assay. J Nat Prod. Published, 01/2021.
  • Bosse GD & Cadeddu R, Floris G, Farero RD, Vigato E, Lee SJ, Zhang T, Gaikwad NW, Keefe KA, Phillips PE, Bortolato M, Peterson RT (2021). The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder. J Clin Invest. Published, 04/13/2021.
  • Paguigan ND & Tun JO, Leavitt LS, Lin Z, Chase K, Dowell C, Deering-Rice CE, Lim AL, Karthikeyan M, Hughen RW, Zhang J, Peterson RT, Reilly CA, Light AR, Raghuraman S, McIntosh JM, Olivera BM, Schmidt EW (2021). Nicotinic Acetylcholine Receptor Partial Antagonist Polyamides from Tunicates and Their Predatory Sea Slugs. ACS Chem Neurosci. Published, 01/2021.
  • Parvez S & Herdman C, Beerens M, Chakraborti K, Harmer ZP, Yeh JJ, MacRae CA, Yost HJ, Peterson RT (2021). MIC-Drop: A platform for large-scale in vivo CRISPR screens. Science. Published, 01/2021.
  • Geng Y & Peterson RT (2021). Rapid Mounting of Zebrafish Larvae for Brain Imaging. Zebrafish. Published, 12/2021.
  • Carmack SA & Vendruscolo JCM, Adrienne McGinn M, Miranda-Barrientos J, Repunte-Canonigo V, Bosse GD, Mercatelli D, Giorgi FM, Fu Y, Hinrich AJ, Jodelka FM, Ling K, Messing RO, Peterson RT, Rigo F, Edwards S, Sanna PP, Morales M, Hastings ML, Koob GF, Vendruscolo LF (2022). Corticosteroid sensitization drives opioid addiction. Mol Psychiatry. Published, 05/2022.
  • Nielson JR & Nath AK, Doane KP, Shi X, Lee J, Tippetts EG, Saha K, Morningstar J, Hicks KG, Chan A, Zhao Y, Kelly A, Hendry-Hofer TB, Witeof A, Sips PY, Mahon S, Bebarta VS, Davisson VJ, Boss GR, Rutter J, MacRae CA, Brenner M, Gerszten RE, Peterson RT (2022). Glyoxylate protects against cyanide toxicity through metabolic modulation. Sci Rep. Published, 03/23/2022.
  • Hope KA & Berman AR, Peterson RT, Chow CY (2022). An in vivo drug repurposing screen and transcriptional analyses reveals the serotonin pathway and GSK3 as major therapeutic targets for NGLY1 deficiency. PLoS Genet. Published, 06/02/2022.
  • Bebarta VS & Shi X, Zheng S, Hendry-Hofer TB, Severance CC, Behymer MM, Boss GR, Mahon S, Brenner M, Knipp GT, Davisson VJ, Peterson RT, MacRae CA, Rutter J, Gerszten RE, Nath AK (2023). Intramuscular Administration of Glyoxylate Rescues Swine from Lethal Cyanide Poisoning and Ameliorates the Biochemical Sequalae of Cyanide Intoxication. Toxicol Sci. Published, 01/2023.
  • Behymer MM & Mo H, Fujii N, Suresh V, Chan A, Lee J, Nath AK, Saha K, Mahaon SB, Brenner M, MacRae CA, Peterson R, Boss GR, Knipp GT, Davisson VJ (2023). Identification of Platinum (II) Sulfide Complexes Suitable as Intramuscular Cyanide Countermeasures. Chemical Research in Toxicology. Published, 01/2023.
  • Geng Y & Zhang T, Alonzo IG, Godar SC, Yates C, Pluimer BR, Harrison DL, Nath AK, Yeh JJ, Drummond IA, Bortolato M, Peterson RT (2022). Top2a promotes the development of social behavior via PRC2 and H3K27me3. Sci Adv. Published, 01/2022.
  • Geng Y & Yates C, Peterson RT (2023). Social behavioral profiling by unsupervised deep learning reveals a stimulative effect of dopamine D3 agonists on zebrafish sociality. Cell Rep Methods. Published, 01/05/2023.
  • Zhang T & Alonzo I, Stubben C, Geng Y, Herdman C, Chandler N, Doane KP, Pluimer BR, Trauger SA, Peterson RT (2023). A zebrafish model of combined saposin deficiency identifies acid sphingomyelinase as a potential therapeutic target. Dis Model Mech. Published, 07/01/2023.
  • Pluimer BR & Harrison DL, Boonyavairoje C, Prinssen EP, Rogers-Evans M, Peterson RT, Thyme SB, Nath AK (2023). Behavioral analysis through the lifespan of disc1 mutant zebrafish identifies defects in sensorimotor transformation. iScience. Published, 06/14/2023.
  • Sampieri A & Padilla-Flores T, Thawani AR, Lam PY, Fuchter MJ, Peterson R, Vaca L (2023). The conducting state of TRPA1 modulates channel lateral mobility. Cell Calcium. Published, 12/2023.
  • Behymer MM & Mo H, Fujii N, Suresh V, Arzumanian AS, Chan A, Nath AK, McCain R, MacRae CA, Peterson R, Boss GR, Davisson VJ, Knipp GT (2023). Investigating the Replacement of Carboxylates with Carboxamides to Modulate the Safety and Efficacy of Platinum(II) Thioether Cyanide Scavengers. Toxicol Sci. Published, 11/11/2023.
  • Cassar S & Adatto I, Freeman JL, Gamse JT, Iturria I, Lawrence C, Muriana A, Peterson RT, Van Cruchten S, Zon LI (2020). Use of Zebrafish in Drug Discovery Toxicology. Chem Res Toxicol. Published, 01/2020.
  • Zhang T & Peterson RT (2020). Modeling Lysosomal Storage Diseases in the Zebrafish. Front Mol Biosci. Published, 01/2020.
  • Schenk S & Bosse GD, Peterson RT (2020). Zebrafish models of drug addiction. Psychobiological Issues in Substance Use and Misuse. Published, 01/2020.
  • Jin YN & Peterson RT (2021). Chemical Genetics: Manipulating the Germline with Small Molecules. Methods Mol Biol. Published, 01/2021.
  • Shcheglovitov A & Peterson RT (2021). Screening Platforms for Genetic Epilepsies-Zebrafish, iPSC-Derived Neurons, and Organoids. Neurotherapeutics. Published, 09/30/2021.
  • MacRae CA & Peterson RT (2022). Zebrafish as a Mainstream Model for In Vivo Systems Pharmacology and Toxicology. Annu Rev Pharmacol Toxicol. Published, 09/23/2022.
  • Parvez S & Brandt ZJ, Peterson RT (2024). Large-scale F0 CRISPR screens in vivo using MIC-Drop. Methods Mol Biol. Accepted, 01/2024.
  • Parvez S & Zhang T, Peterson RT (2024). Scalable CRISPR Screens in Zebrafish Using MIC-Drop. Methods Mol Biol. Accepted, 01/2024.