Joshua Knowles

Joshua W. Knowles, MD, PhD, Associate Professor, Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine

Research Description: Dr. Knowles' research has been centered on understanding the genetic basis for insulin resistance (IR). He has helped to lead a large international consortium (GENESIS) that has identified novel insulin sensitivity genes and is focused on understanding the causal mechanisms for these genes. He has also pioneered the creation of induced pluripotent cell models of IR to serve as a resource for the greater scientific community. Knowles is also a clinician with a strong interest in understanding the cardiovascular implications of insulin resistance specifically statin-associated type 2 diabetes. He has had long-term and productive collaborations with other members of SDRC, detailed below and in his biosketch. Dr. Knowles is co-leader of the Metabolism and Signaling in Diabetes Research Affinity Group of SDRC. 

Selected relevant publications (Stanford DRC members in BOLD):

  1. Shahbazi M, Cundiff P, Zhou W, Lee P, Patel A, D’Souza SL, Abbasi F, Quertermous T, Knowles JW. The role of insulin as a key regulator of seeding, proliferation, and mRNA transcription of human pluripotent stem cells. Stem Cell Res Ther 10(1): 228, 2019. [cites SDRC and DGAC support] 

  2. Harati H, Zanetti D, Rao A, Gustafsson S, Perez M, Ingelsson E, Knowles JW. No evidence of a causal association of type 2 diabetes and glucose metabolism with atrial fibrillation. Diabetologia 62: 800-804, 2019.  

  3. Cook NL, Pjanic M, Emmerich AG, Rao AS, Hetty S, Knowles JW, Quertermous T, Castillejo-López C, Ingelsson E. CRISPR-Cas9-mediated knockout of SPRY2 in human hepatocytes leads to increased glucose uptake and lipid droplet accumulation. BMC Endocr Disord. 2019 Oct 29;19(1):115. doi: 10.1186/s12902-019-0442-8. PMID: 31664995; PMCID: PMC6820957. 

  4. Fathzadeh M, Li J, Rao A, Cook N, Chennamsetty I, Seldin M, Zhou X, Sangwung P, Gloudemans MJ, Keller M, Attie A, Yang J, Wabitsch M, Carcamo-Orive I, Tada Y, Lusis AJ, Shin MK, Molony CM, McLaughlin T, Reaven G, Montgomery SB, Reilly D, Quertermous T, Ingelsson E, Knowles JW. FAM13A affects body fat distribution and adipocyte function. Nat Commun. 2020 Mar 19;11(1):1465. doi: 10.1038/s41467-020-15291-z. PMID: 32193374; PMCID: PMC7081215. [cites SDRC core support]  

  5. Kho PF, Wary N, Zanetti D, Abbasi F, Knowles JW, Panyard DJ, Watson KT; RISC Investigators; Stell L, Lazzeroni LC, Gustafsson S, Lind L, Petrie JR, Assimes TL. Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations. Metabolism. 2025 Aug;169:156263. doi: 10.1016/j.metabol.2025.156263. Epub 2025 Apr 11. PMID: 40221021; PMCID: PMC12170150. 

  6. Justesen JM, Venkataraman G, Tanigawa Y, Li R, Hastie T, Tibshirani R, Knowles JW, Rivas MA. Genetics of cardiometabolic disease progression. medRxiv [Preprint]. 2025 Feb 3:2025.02.01.25321518. doi: 10.1101/2025.02.01.25321518. PMID: 39974115; PMCID: PMC11838626. 

  7. Luxama JW, Knowles JW. Many Journeys Originating at the Same Source to Arrive at Solutions to the Common Problem of High Lipoprotein(a). Circ Genom Precis Med. 2025 Apr;18(2):e005126. doi: 10.1161/CIRCGEN.125.005126. Epub 2025 Mar 25. PMID: 40130305; PMCID: PMC11999797. 

  8. Lee BN, Taylor HJ, Cipriani F, Narisu N, Robertson CC, Swift AJ, Sinha N, Yan T, Bonnycastle LL, Dale N, Butt A, Parsaud H, Semrau S; NYSCF Global Stem Cell Array Team; GENESiPS Consortium; iPSCORE Consortium; Knowles JW, Carcamo-Orive I, D'Antonio-Chronowska A, Frazer KA, Biesecker LG, Noggle S, Erdos MR, Paull D, Collins FS, Taylor DL. Genetics of growth rate in induced pluripotent stem cells. bioRxiv [Preprint]. 2025 Jul 3:2025.07.02.662844. doi: 10.1101/2025.07.02.662844. PMID: 40631191; PMCID: PMC12236597. 

  9. Moncal KK, Najmi LA, Gupta R, Ramarao M, Knowles JW, Park CY, Durmus NG. Label-Free Detection of Lipid Accumulation in Cells Using Magnetic Levitation. Adv Biol (Weinh). 2025 Jul;9(7):e2200142. doi: 10.1002/adbi.202200142. Epub 2025 Feb 27. PMID: 40017001. 

  10. Zhao L, Zhou J, Abbasi F, Fathzadeh M, Knowles JW, Leung LLK, Morser J. Chemerin in Participants with or without Insulin Resistance and Diabetes. Biomedicines. 2024 Apr 22;12(4):924. doi: 10.3390/biomedicines12040924. PMID: 38672278; PMCID: PMC11048116. 

  11. Yu GZ, Krentz NAJ, Bentley L, Zhao M, Paphiti K, Sun H, Honecker J, Nygård M, Dashti H, Bai Y, Reid M, Thaman S, Wabitsch M, Rajesh V, Yang J, Mattis KK, Abaitua F, Casero R, Hauner H, Knowles JW, Wu JY, Mandrup S, Claussnitzer M, Svensson KJ, Cox RD, Gloyn AL. Loss of RREB1 reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes. bioRxiv [Preprint]. 2024 Jul 31:2024.07.30.605923. doi: 10.1101/2024.07.30.605923. PMID: 39131393; PMCID: PMC11312556. 

  12. Shetty NS, Gaonkar M, Patel N, Knowles JW, Natarajan P, Arora G, Arora P. Trends of Lipid Concentrations, Awareness, Evaluation, and Treatment in Severe Dyslipidemia in US Adults. Mayo Clin Proc. 2024 Feb;99(2):271-282. doi: 10.1016/j.mayocp.2023.09.016. Epub 2024 Jan 6. PMID: 38189687; PMCID: PMC10873035. 

  13. Zanetti D, Stell L, Gustafsson S, Abbasi F, Tsao PS, Knowles JW; RISC Investigators; Zethelius B, Ärnlöv J, Balkau B, Walker M, Lazzeroni LC, Lind L, Petrie JR, Assimes TL. Plasma proteomic signatures of a direct measure of insulin sensitivity in two population cohorts. Diabetologia. 2023 Sep;66(9):1643-1654. doi: 10.1007/s00125-023-05946-z. Epub 2023 Jun 17. PMID: 37329449; PMCID: PMC10390625. 

  14. Cuchel M, Lee PC, Hudgins LC, Duell PB, Ahmad Z, Baum SJ, Linton MF, de Ferranti SD, Ballantyne CM, Larry JA, Hemphill LC, Kindt I, Gidding SS, Martin SS, Moriarty PM, Thompson PP, Underberg JA, Guyton JR, Andersen RL, Whellan DJ, Benuck I, Kane JP, Myers K, Howard W, Staszak D, Jamison A, Card MC, Bourbon M, Chora JR, Rader DJ, Knowles JW, Wilemon K, McGowan MP. Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry. J Am Heart Assoc. 2023 May 2;12(9):e029175. doi: 10.1161/JAHA.122.029175. Epub 2023 Apr 29. Erratum in: J Am Heart Assoc. 2023 Jun 6;12(11):e027706. doi: 10.1161/JAHA.122.027706. PMID: 37119068; PMCID: PMC10227232. 

  15. Kim D, Alshuwaykh O, Dennis BB, Cholankeril G, Knowles JW, Ahmed A. Chronic liver disease-related mortality in diabetes before and during the COVID-19 in the United States. Dig Liver Dis. 2023 Jan;55(1):3-10. doi: 10.1016/j.dld.2022.09.006. Epub 2022 Sep 29. PMID: 36182570; PMCID: PMC9534558. 

  16. Marwaha S, Knowles JW, Ashley EA. A guide for the diagnosis of rare and undiagnosed disease: beyond the exome. Genome Med. 2022 Feb 28;14(1):23. doi: 10.1186/s13073-022-01026-w. PMID: 35220969; PMCID: PMC8883622. 

  17. Chora JR, Iacocca MA, Tichý L, Wand H, Kurtz CL, Zimmermann H, Leon A, Williams M, Humphries SE, Hooper AJ, Trinder M, Brunham LR, Costa Pereira A, Jannes CE, Chen M, Chonis J, Wang J, Kim S, Johnston T, Soucek P, Kramarek M, Leigh SE, Carrié A, Sijbrands EJ, Hegele RA, Freiberger T, Knowles JW, Bourbon M; ClinGen Familial Hypercholesterolemia Expert Panel. The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification. Genet Med. 2022 Feb;24(2):293-306. doi: 10.1016/j.gim.2021.09.012. Epub 2021 Nov 30. PMID: 34906454. 

  18. Kim DS, Gloyn AL, Knowles JW. Genetics of Type 2 Diabetes: Opportunities for Precision Medicine: JACC Focus Seminar. J Am Coll Cardiol. 2021 Aug 3;78(5):496-512. doi: 10.1016/j.jacc.2021.03.346. PMID: 34325839; PMCID: PMC8328195. 

  19. Katz SF, Rodriguez F, Knowles JW. Health disparities in cardiometabolic risk among Black and Hispanic youth in the United States. Am J Prev Cardiol. 2021 Mar 23;6:100175. doi: 10.1016/j.ajpc.2021.100175. PMID: 34327498; PMCID: PMC8315636. 

  20. Wand H, Knowles JW, Clarke SL. The need for polygenic score reporting standards in evidence-based practice: lipid genetics use case. Curr Opin Lipidol. 2021 Apr 1;32(2):89-95. doi: 10.1097/MOL.0000000000000733. PMID: 33538426; PMCID: PMC7962796. 

  21. Abbasi F, Lamendola C, Harris CS, Harris V, Tsai MS, Tripathi P, Abbas F, Reaven GM, Reaven PD, Snyder MP, Kim SH, Knowles JW. Statins Are Associated With Increased Insulin Resistance and Secretion. Arterioscler Thromb Vasc Biol. 2021 Nov;41(11):2786-2797. doi: 10.1161/ATVBAHA.121.316159. Epub 2021 Aug 26. PMID: 34433298; PMCID: PMC8551023. 

  22. Sarraju A, Valencia A, Knowles JW, Maron DJ, Rodriguez F. Diverse Racial/Ethnic Group Underreporting and Underrepresentation in High-Impact Cholesterol Treatment Trials. Circulation. 2021 Jun 15;143(24):2409-2411. doi: 10.1161/CIRCULATIONAHA.120.050034. Epub 2021 Jun 14. PMID: 34125567; PMCID: PMC8210460. 

  23. Bonder MJ, Smail C, Gloudemans MJ, Frésard L, Jakubosky D, D'Antonio M, Li X, Ferraro NM, Carcamo-Orive I, Mirauta B, Seaton DD, Cai N, Vakili D, Horta D, Zhao C, Zastrow DB, Bonner DE; HipSci Consortium; iPSCORE consortium; Undiagnosed Diseases Network; PhLiPS consortium; Wheeler MT, Kilpinen H, Knowles JW, Smith EN, Frazer KA, Montgomery SB, Stegle O. Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics. Nat Genet. 2021 Mar;53(3):313-321. doi: 10.1038/s41588-021-00800-7. Epub 2021 Mar 4. PMID: 33664507; PMCID: PMC7944648. 

  24. Balliu B, Carcamo-Orive I, Gloudemans MJ, Nachun DC, Durrant MG, Gazal S, Park CY, Knowles DA, Wabitsch M, Quertermous T, Knowles JW, Montgomery SB. An integrated approach to identify environmental modulators of genetic risk factors for complex traits. Am J Hum Genet. 2021 Oct 7;108(10):1866-1879. doi: 10.1016/j.ajhg.2021.08.014. Epub 2021 Sep 27. PMID: 34582792; PMCID: PMC8546041. 

  25. Haider N, Lebastchi J, Jayavelu AK, Batista TM, Pan H, Dreyfuss JM, Carcamo-Orive I, Knowles JW, Mann M, Kahn CR. Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex. J Clin Invest. 2021 Nov 1;131(21):e151818. doi: 10.1172/JCI151818. PMID: 34506305; PMCID: PMC8553553. 

  26. Jiang Z, Zhao M, Voilquin L, Jung Y, Aikio MA, Sahai T, Dou FY, Roche AM, Carcamo-Orive I, Knowles JW, Wabitsch M, Appel EA, Maikawa CL, Camporez JP, Shulman GI, Tsai L, Rosen ED, Gardner CD, Spiegelman BM, Svensson KJ. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Cell Metab. 2021 Sep 7;33(9):1836-1852.e11. PMID: 34348115; PMCID: PMC8429235. 

  27. Rowland CM, Abbasi F, Shiffman D, Knowles JW, McPhaul MJ. The relationship between insulin resistance and ion mobility lipoprotein fractions. Am J Prev Cardiol. 2022 Dec 25;13:100457. doi: 10.1016/j.ajpc.2022.100457. PMID: 36619297; PMCID: PMC9816659. 

  28. Bielczyk-Maczynska E, Zhao M, Zushin PH, Schnurr TM, Kim HJ, Li J, Nallagatla P, Sangwung P, Park CY, Cornn C, Stahl A, Svensson KJ, Knowles JW. G protein-coupled receptor 151 regulates glucose metabolism and hepatic gluconeogenesis. Nat Commun. 2022 Dec 1;13(1):7408. 

  29. Schnurr TM, Katz SF, Justesen JM, O'Sullivan JW, Saliba-Gustafsson P, Assimes TL, Carcamo-Orive I, Ahmed A, Ashley EA, Hansen T, Knowles JW. Interactions of physical activity, muscular fitness, adiposity, and genetic risk for NAFLD. Hepatol Commun. 2022 Jul;6(7):1516-1526. PMID: 35293152; PMCID: PMC9234625. 

  30. Gloudemans MJ, Balliu B, Nachun D, Schnurr TM, Durrant MG, Ingelsson E, Wabitsch M, Quertermous T, Montgomery SB, Knowles JW, Carcamo-Orive I. Integration of genetic colocalizations with physiological and pharmacological perturbations identifies cardiometabolic disease genes. Genome Med. 2022 Mar 15;14(1):31. doi: 10.1186/s13073-022-01036-8. PMID: 35292083; PMCID: PMC8925074. 

  31. Bielczyk-Maczynska E, Sharma D, Blencowe M, Saliba Gustafsson P, Gloudemans MJ, Yang X, Carcamo-Orive I, Wabitsch M, Svensson KJ, Park CY, Quertermous T, Knowles JW, Li J. A single-cell CRISPRi platform for characterizing candidate genes relevant to metabolic disorders in human adipocytes. Am J Physiol Cell Physiol. 2023 Sep 1. PMID: 37486064; PMCID: PMC10635647. 

  32. Li J, Jin C, Gustafsson S, Rao A, Wabitsch M, Park CY, Quertermous T, Knowles JW, Bielczyk-Maczynska E. Single-cell transcriptome dataset of human and mouse in vitro adipogenesis models. Sci Data. 2023 PMID: 37328521; PMCID: PMC10275883. 

  33. Xiao S, Li VL, Lyu X, Chen X, Wei W, Abbasi F, Knowles JW, Tung AS, Deng S, Tiwari G, Shi X, Zheng S, Farrell L, Chen ZZ, Taylor KD, Guo X, Goodarzi MO, Wood AC, Chen YI, Lange LA, Rich SS, Rotter JI, Clish CB, Tahir UA, Gerszten RE, Benson MD, Long JZ. Lac-Phe mediates the effects of metformin on food intake and body weight. Nat Metab. 2024 Apr;6(4):659-669. doi: 10.1038/s42255-024-00999-9. Epub 2024 Mar 18. PMID: 38499766; PMCID: PMC11062621. 

  34. Zhang P, Munier JJ, Wiese CB, Vergnes L, Link JC, Abbasi F, Ronquillo E, Scheker K, Muñoz A, Kuang YL, Theusch E, Lu M, Sanchez G, Oni-Orisan A, Iribarren C, McPhaul MJ, Nomura DK, Knowles JW, Krauss RM, Medina MW, Reue K. X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction. Nat Commun. 2024 Jul 2;15(1):5571. doi: 10.1038/s41467-024-49764-2. PMID: 38956041; PMCID: PMC11219728. 

  35. Nagy N, Czepiel KS, Kaber G, Stefanovski D, Hargil A, Pennetzdorfer N, Targ R, Reghupaty SC, Wight TN, Vernon RB, Hull-Meichle RL, Marshall P, Medina CO, Martinez H, Kalinowski A, Paladini RD, Garantziotis S, Knowles JW, Bollyky PL. Hymecromone Promotes Longevity and Insulin Sensitivity in Mice. Cells. 2024 Oct 18;13(20):1727. doi: 10.3390/cells13201727. PMID: 39451245; PMCID: PMC11506560. 

  36. Saliba-Gustafsson P, Justesen JM, Ranta A, Sharma D, Bielczyk-Maczynska E, Li J, Najmi LA, Apodaka M, Aspichueta P, Björck HM, Eriksson P, Schurr TM, Franco-Cereceda A, Gloudemans M, Mujica E, den Hoed M, Assimes TL, Quertermous T, Carcamo-Orive I, Park CY, Knowles JW. A functional genomic framework to elucidate novel causal metabolic dysfunction-associated fatty liver disease genes. Hepatology. 2025 Jul 1;82(1):165-183. doi: 10.1097/HEP.0000000000001066. Epub 2024 Aug 27. PMID: 39190705; PMCID: PMC11865357.