LOUIS R BARROWS portrait
  • Professor, Pharmacology And Toxicology
801-581-4547

Research Interests

My laboratory is dedicated to the discovery of new anti-cancer and anti-infective agents. Much of what we do can be considered natural products drug discovery. We identify new drug leads based on their novel chemical structure or mechanism of action. Extracts of macro- and microorganisms from coral reefs and tropical rain forests provide the new molecules we isolate and evaluate. Determination of the molecular actions of new molecules and determination of the precise cellular consequences of their activity is often the basis of student doctoral projects. We take bioactive organisms and molecules all the way from the source to the sequencing gel, and then into animal models of human disease.

Our recent major projects are focused mostly around antimicrobial drug discovery. We are developing models to assess drug action on intracellular bacterial pathogens, such as Mycobacteria or Francisella, in order to understand pathogen and host cell responses in the context of drug efficacy. Other models we are developing involve HIV- 1/TB coinfection, in which we can define selective antiviral or antibacterial drug action on the various host cell populations of singly-, doubly- or un-infected macrophages in the co-culture systems. These model systems allow us to identify new and unanticipated drug activities that serve as the basis for further research. We are also using these co-culture model systems to inform omics analyses of patient samples from TB or HIV/TB infected individuals. While this is just beginning, we have been able to generate single cell RNA sequencing libraries from nodal granulomas of TB patients in Papua New Guinea. Key transcriptional markers identified in our model systems are helping to understand cellular composition and infection status of these patients. It is hoped that such transcriptomic and genomic analysis will also identify drug resistance in these patients and personalize their therapeutic regimen.

Languages

  • English, fluent.

Publications

  • Single Cell Analysis of Peripheral TB-Associated Granulomatous Lymphadenitis. Moos PJ, Carey AF, Joseph J, Kialo S, Norrie J, Moyarelce JM, Amof A, Nogua H, Lim AL, Barrows LR. bioRxiv [Preprint]. 2024 Jun 26:2024.05.28.596301. doi: 10.1101/2024.05.28.596301. PMID: 38853908 Free PMC article. Preprint. Published, 06/26/2024.
  • Resistance mechanisms for Gram-negative bacteria-specific lipopeptides, turnercyclamycins, differ from that of colistin. Lim AL, Miller BW, Lin Z, Fisher MA, Barrows LR, Haygood MG, Schmidt EW. Microbiol Spectr. 2023 Dec 12;11(6):e0230623. doi: 10.1128/spectrum.02306-23. Epub 2023 Oct 26. PMID: 37882570 Free PMC article. Published, 12/12/2023.
  • HIV-1 provirus transcription and translation in macrophages differs from pre-integrated cDNA complexes and requires E2F transcriptional programs. Lim AL, Moos P, Pond CD, Larson EC, Martins LJ, Szaniawski MA, Planelles V, Barrows LR. Virulence. 2022 Dec;13(1):386-413. doi: 10.1080/21505594.2022.2031583. PMID: 35166645 Free PMC article. Published, 12/2022.
  • Flavonoids and Phenols, the Potential Anti-Diabetic Compounds from Bauhinia strychnifolia Craib. Stem. Praparatana R, Maliyam P, Barrows LR, Puttarak P. Molecules. 2022 Apr 7;27(8):2393. doi: 10.3390/molecules27082393. PMID: 35458587 Free PMC article. Published, 04/07/2022.
  • Histone deacetylase inhibition reduces deleterious cytokine release induced by ingenol stimulation. Larragoite ET, Nell RA, Martins LJ, Barrows LR, Planelles V, Spivak AM. Biochem Pharmacol. 2022 Jan;195:114844. doi: 10.1016/j.bcp.2021.114844. Epub 2021 Nov 18. PMID: 34801521 Free PMC article. Published, 01/2022.
  • Shipworm symbiosis ecology-guided discovery of an antibiotic that kills colistin-resistant Acinetobacter. Miller BW, Lim AL, Lin Z, Bailey J, Aoyagi KL, Fisher MA, Barrows LR, Manoil C, Schmidt EW, Haygood MG. Cell Chem Biol. 2021 Nov 18;28(11):1628-1637.e4. doi: 10.1016/j.chembiol.2021.05.003. Epub 2021 Jun 18. PMID: 34146491 Free PMC article. Published, 11/18/2021.
  • Unifying the Aminohexopyranose- and Peptidyl-Nucleoside Antibiotics: Implications for Antibiotic Design. Serrano CM, Kanna Reddy HR, Eiler D, Koch M, Tresco BIC, Barrows LR, VanderLinden RT, Testa CA, Sebahar PR, Looper RE. Angew Chem Int Ed Engl. 2020 Jul 6;59(28):11330-11333. doi: 10.1002/anie.202003094. Epub 2020 May 11. PMID: 32342623 Free PMC article. Published, 06/06/2020.
  • Pyrrolocin C and equisetin inhibit bacterial acetyl-CoA carboxylase. Larson EC, Lim AL, Pond CD, Craft M, Čavužić M, Waldrop GL, Schmidt EW, Barrows LR. PLoS One. 2020 May 29;15(5):e0233485. doi: 10.1371/journal.pone.0233485. eCollection 2020. PMID: 32470050 Free PMC article. Published, 05/29/2020.
  • Accessing chemical diversity from the uncultivated symbionts of small marine animals. Smith TE, Pond CD, Pierce E, Harmer ZP, Kwan J, Zachariah MM, Harper MK, Wyche TP, Matainaho TK, Bugni TS, Barrows LR, Ireland CM, Schmidt EW. Nat Chem Biol. 2018 Feb;14(2):179-185. doi: 10.1038/nchembio.2537. Epub 2018 Jan 1. PMID: 29291350 Free PMC article. Published, 02/2018.
  • Mycobacterium tuberculosis reactivates latent HIV-1 in T cells in vitro. Larson EC, Novis CL, Martins LJ, Macedo AB, Kimball KE, Bosque A, Planelles V, Barrows LR. PLoS One. 2017 Sep 26;12(9):e0185162. doi: 10.1371/journal.pone.0185162. eCollection 2017. PMID: 28949981 Free PMC article. Published, 09/26/2017.