Faculty & Staff

Research Summary

Dr. Eckfeldt is a faculty investigator in the Advanced Research and Diagnostics Laboratory (ARDL), which provides central laboratory testing services for large, NIH-funded multi-center clinical trials. Through numerous national studies he has established himself as a leading researcher in the area of cardiovascular disease epidemiology, particularly the role lipids and other biomarkers play in cardiovascular diseases. Eckfeldt was principal laboratory investigator for the Hispanic Community Health Study, an NIH-funded multicenter epidemiologic study of U.S. Hispanic/Latino populations, and is the PI for the ancillary Hispanic Community Children's Health Study / Study of Latino Youth (SOL Youth), a multicenter study of Hispanic/Latino children living in the U.S. The SOL Youth study is designed to disclose the prevalence and distribution of obesity-promoting lifestyle behaviors, cardio-metabolic risk profiles, and novel biomarkers associated with obesity and insulin resistance.

In recent years Eckfeldt has focused mainly on kidney disease. He is a co-investigator with the Chronic Kidney Disease Biomarkers Consortium (CKD-BioCon). CKD-BioCON is a longitudinal study involving multiple universities with NIH’s National Institute of Diabetes and Digestive and Kidney Diseases that seeks to discover, develop, validate and qualify biomarkers based on biosamples from well-characterized CKD patients. He also serves as co-PI for the Preventing Early Renal Loss in Diabetes (PERL) consortium. The consortium has undertaken a multi-center, double-blind, placebo-controlled, randomized clinical trial aimed at evaluating the efficacy of allopurinol in preventing kidney function loss in individuals with type 1 diabetes. In addition, Eckfeldt is a co-investigator and the central laboratory director in the chronic kidney disease epidemiology collaboration (CKD-EPI). In this capacity he tests protein biomarkers such as cystatin C, an important marker for measuring the glomerular filtration rate, which indicates how well the kidneys are working.

Dr. Eckfeldt has long had an interest in assuring the reliability and long-term stability of assay results in large-scale epidemiological observational and interventional research studies. In addition he has sought to further the standardization and harmonization of clinical laboratories and inter-laboratory comparability through committee work at the College of American Pathologists (CAP) and working group participation at the International Standards Organization (ISO).

Publications

PubMed

• Chen N, Shi H, Zhang L, Zuo L, Xie J, Xie D, Karger AB, Miao S, Ren H, Zhang W, Wang W, Pan Y, Minji W, Sui Z, Okparavero A, Simon A, Chaudhari J, Eckfeldt JH, Inker LA, Levey AS. GFR Estimation Using a Panel of Filtration Markers in Shanghai and Beijing. Kidney Med. 2020;2(2):172-180. Published 2020 Jan 31. doi:10.1016/j.xkme.2019.11.004.
• Seegmiller JC, Eckfeldt JH, Lieske JC. Challenges in Measuring Glomerular Filtration Rate: A Clinical Laboratory Perspective. Adv Chronic Kidney Dis. 2018 Jan;25(1):84-92. doi: 10.1053/j.ackd.2017.10.006
• Schwartz GJ, Wang H, Erway B, Nordin G, Seegmiller J, Lieske JX, Bäck S-E, Miller WG, Eckfeldt JH. Multicenter Laboratory Comparison of Iohexol Measurement. The Journal of Applied Laboratory Medicine Mar 2018, 2 (5) 711-724; DOI: 10.1373/jalm.2017.024240 http://jalm.aaccjnls.org/content/2/5/711
• Karger AB, Inker LA, Coresh J, Levey AS, Eckfeldt JH. Novel Filtration Markers for GFR Estimation. EJIFCC 2017 Dec 19:28(4):277-288.eCollection 2017 Dec. https://www.ncbi.nlm.nih.gov/pubmed/29333147
• Eckfeldt JH, Karger AB, Miller WG, Rynders GP, Inker LA. Performance in measurement of serum cystatin C by laboratories participating in the college of american pathologists 2014 CYS survey. Arch Pathol Lab Med 2015;139:888-893.

Bio

Dr. Karger is a member of the Division of Molecular Pathology and Genomics and a faculty investigator at the Advanced Research and Diagnostic Laboratory (ARDL). She has multiple research interests including studying immune responses to COVID-19 infection and vaccines, predicting and delaying the progression of chronic kidney disease, and studying cardiovascular and kidney disease complications in patients with type 1 diabetes. Dr. Karger currently serves as Program Director and Principal Investigator for one of four federally funded Serological Sciences Network (SeroNet) Capacity Building Centers, which has been tasked with developing serological assays to test for COVID-19 antibodies, and is conducting research studies to better understand the immune response to COVID-19 infection and vaccination. Additionally, she has been appointed as co-chair of the SeroNet Serology Assays Ops Group. Dr. Karger also serves as Director of the Central Laboratory for the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), which tests biomarkers such as creatinine, cystatin C, beta-2 microglobulin and beta-trace protein to improve GFR estimating equations. Improved GFR estimates give clinicians the ability to detect disease progression at earlier stages. In addition, she serves as co-investigator for the Epidemiology of Diabetes Interventions and Complications trial (EDIC) and co-director of the Biomedical Assay Laboratory for the Division of Intramural Population Health Research at the National Institute of Child Health and Human Development (NICHD). Previously, Dr. Karger served as a principal investigator with the Preventing Early Renal Loss in Diabetes (PERL) consortium. The consortium undertook a multi-center, double-blind, placebo-controlled, randomized clinical trial aimed at evaluating the efficacy of allopurinol in preventing kidney function loss in individuals with type 1 diabetes; the trial found no evidence of benefit from serum urate reduction with allopurinol.

Research Summary

Publications

• Garg PK, Guan W, Nomura S, Weir NL, Karger AB, Duprez D, Tsai MY. Associations of plasma omega-3 and omega-6 pufa levels with arterial elasticity: the multi-ethnic study of atherosclerosis. Eur J Clin Nutr. 2022 Jun 9. doi: 10.1038/s41430-022-01172-9.
• Figueiredo JC, Hirsch FR, Kushi LH, Nembhard WN, Crawford JM, Mantis N, Finster L, Merin NM, Merchant A, Reckamp KL, Melmed GY, Braun J, McGovern D, Parekh S, Corley DA, Zohoori N, Amick BC, Du R, Gregersen PK, Diamond B, Taioli E, Sariol C, Espino A, Weiskopf D, Gifoni A, Brien J, Hanege W, Lipsitch M, Zidar DA, Scheck McAlearney A, Wajnberg A, LaBaer J, Yvonne Lewis E, Binder RA, Moormann AM, Forconi C, Forrester S, Batista J, Schieffelin J, Kim D, Biancon G, VanOudenhove J, Halene S, Fan R, Barouch DH, Alter G, Pinninti S, Boppana SB, Pati SK, Latting M, Karaba AH, Roback J, Sekaly R, Neish A, Brincks AM, Granger DA, Karger AB, Thyagarajan B, Thomas SN, Klein SL, Cox AL, Lucas T, Furr-Holden D, Key K, Jones N, Wrammerr J, Suthar M, Yu Wong S, Bowman NM, Simon V, Richardson LD, McBride R, Krammer F, Rana M, Kennedy J, Boehme K, Forrest C, Granger SW, Heaney CD, Knight Lapinski M, Wallet S, Baric RS, Schifanella L, Lopez M, Fernández S, Kenah E, Panchal AR, Britt WJ, Sanz I, Dhodapkar M, Ahmed R, Bartelt LA, Markmann AJ, Lin JT, Hagan RS, Wolfgang MC, Skarbinski J. Mission, organization, and future direction of the Serological Sciences Network for COVID-19 (SeroNet) epidemiologic cohort studies. Open Forum Infect Dis. 2022 Apr 27;9(6):ofac171. doi: 10.1093/ofid/ofac171.
• Karger AB, Brien JD, Christen JM, Dhakal S, Kemp TJ, Klein SL, Pinto LA, Premkumar L, Roback JD, Binder RA, Boehme KW, Boppana S, Cordon-Cardo C, Crawford JM, Daiss JL, Dupuis AP 2nd, Espino AM, Firpo-Betancourt A, Forconi C, Forrest JC, Girardin RC, Granger DA, Granger SW, Haddad NS, Heaney CD, Hunt DT, Kennedy JL, King CL, Krammer F, Kruczynski K, LaBaer J, Lee FE, Lee WT, Liu SL, Lozanski G, Lucas T, Mendu DR, Moormann AM, Murugan V, Okoye NC, Pantoja P, Payne AF, Park J, Pinninti S, Pinto AK, Pisanic N, Qiu J, Sariol CA, Simon V, Song L, Steffen TL, Stone ET, Styer LM, Suthar MS, Thomas SN, , Wajnberg A, Yates JL, Sobhani K. The Serological Sciences Network (SeroNet) for COVID-19: Depth and breadth of serology assays and plans for assay harmonization. mSphere. 2022 Jun 15:e0019322. doi: 10.1128/msphere.00193-22.
• Thomas SN, Karger AB, Altawallbeh G, Nelson KM, Jacobs DR Jr, Gorlin J, Barcelo H, Thyagarajan B. Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity. Sci Rep. 2022 May 25;12(1):8890. doi: 10.1038/s41598-022-12869-z
• Perkins BA, Bebu I, Gao X, Karger AB, Hirsch IB, Karanchi H, Molitch ME, Zinman B, Lachin JM, and de Boer IH. Early trajectory of estimated glomerular filtration rate and long-term advanced kidney and cardiovascular complications in type 1 diabetes. Diabetes Care. 2022 Mar 1;45(3):585-593. doi: 10.2337/dc21-1883. PMID: 35015817

Bio

Dr. Killeen is Director of Clinical Laboratories at the University of Minnesota Medical Center, Fairview, Vice Chair for Clinical Affairs in the Department of Laboratory Medicine and Pathology, and a member of the Division of Molecular Pathology and Genomics. He also chairs the College of American Pathologists' Committee on Laboratory Accuracy Surveys and the Instrumentation Resource Committee. The committee monitors the quality of laboratory assays across the country through the distribution, collection and analysis of proficiency testing specimens and brings problems it identifies to the attention of the clinical pathology community.  Dr. Killeen conducts his clinical research through ARDL, a central laboratory for large-scale clinical trials. He is the Principal Investigator for the central laboratory activities of the Systolic Blood Pressure Intervention Trial (SPRINT), an NIH-funded multi-center, randomized clinical trial designed to test whether a treatment program aimed at reducing systolic blood pressure to a lower goal than currently recommended (<120 mm Hg rather than <140 mm Hg) will reduce cardiovascular disease risk. Some 9,300 research subjects have been enrolled in the seven-year study, which ends in 2018. SPRINT investigators believe the study will provide important information on the risks and benefits of intensive blood pressure treatment targets in a range of high-risk participants including those with prior cardiovascular disease, chronic kidney disease, and those age 75 years or older.

Research Summary

Publications

Stoffel M, Greene DN, Beal SG, Foley P, Killeen AA, Shafi H, Terrazas E.  Direct-to-Consumer Testing for Routine Purposes. Clin Chem. 2022 Sep 1;68(9):1121-1127. doi: 10.1093/clinchem/hvac106. PMID: 35971633.

SPRINT Research Group; Lewis CE, Fine LJ, Beddhu S, Cheung AK, Cushman WC, Cutler JA, Evans GW, Johnson KC, Kitzman DW, Oparil S, Rahman M, Reboussin DM, Rocco MV, Sink KM, Snyder JK, Whelton PK, Williamson JD, Wright JT Jr, Ambrosius WT. Final Report of a Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2021 May 20;384(20):1921-1930. doi: 10.1056/NEJMoa1901281. PMID: 34010531.

Garimella PS, Lee AK, Ambrosius WT, Bhatt U, Cheung AK, Chonchol M, Craven T, Hawfield AT, Jotwani V, Killeen A, Punzi H, Sarnak MJ, Wall BM, Ix JH, Shlipak MG. Markers of kidney tubule function and risk of cardiovascular disease events and mortality in the SPRINT trial. Eur Heart J. 2019 Nov 1;40(42):3486-3493. doi: 10.1093/eurheartj/ehz392.

Ginsberg C, Craven TE, Chonchol MB, Cheung AK, Sarnak MJ, Ambrosius WT, Killeen AA, Raphael KL, Bhatt UY, Chen J, Chertow GM, Freedman BI, Oparil S, Papademetriou V, Wall BM, Wright CB, Ix JH, Shlipak MG; SPRINT Research Group. PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT. Clin J Am Soc Nephrol. 2018 Dec 7;13(12):1816-1824. doi: 10.2215/CJN.05390518.

Malhotra R, Craven T, Ambrosius WT, Killeen AA, Haley WE, Cheung AK, Chonchol M, Sarnak M, Parikh CR, Shlipak MG, Ix JH; SPRINT Research Group. Effects of intensive blood pressure lowering on kidney tubule injury in CKD: A longitudinal subgroup analysis in SPRINT. Am J Kidney Dis. 2018 Sep 28. pii: S0272-6386(18)30879-5. doi: 10.1053/j.ajkd.2018.07.015.

Danni Li, Angela Radulescu, Rupendra T. Shrestha, Matthew Root, Amy B. Karger, Anthony A. Killeen, James S. Hodges, Shu-Ling Fan, Angela Ferguson, Uttam Garg, Lori J. Sokoll, Lynn A. Burmeister. Association of biotin ingestion with performance of hormone and nonhormone assays in healthy adults. JAMA 2017.;318(12):1150-1160.doi:10.1001/jama.2017.13705. https://goo.gl/yeqSt

Killeen AA: The Clinical Laboratory in Modern Healthcare. In Kasper D, Fauci A, Longo D, Hauser S, Jameson J, Loscalzo J (eds): Harrison’s Principles of Internal Medicine, 19^th Edition, 2015.

Bio

Dr. Li is a faculty investigator in the Advanced Research and Diagnostic Laboratory (ARDL) where she applies mass spectrometry (MS) to the discovery of biomarkers for diagnosis including for Alzheimer's disease, diabetes, heart disease, and cancers. She was trained in analytical chemistry and in proteomics research using MS technology, particularly in identifying proteomic biomarkers that are clinically relevant and have an impact on patient care. Biomarker discovery is a key area of translational research.Besides identifying biomarkers that may be important in clinical medicine, Dr. Li is addressing several challenges posed by MS technology. One is to develop standard protocols to ensure the reproducibility of biomarkers. Another is to design each study in a way that takes into account the complexity and heterogeneity of biological samples and eliminates potentially confounding factors. A third challenge is data analysis of hundreds or even thousands of biomarkers that are expressed at different levels and identifying those that are clinically significant. Collaboration with trusted experts in engineering, bioinformatics, and biostatistics is necessary for study design and data analysis and interpretation. Li believes biomarker research, increasingly a team effort, can lead to advances in precision medicine and better clinical outcomes for patients.

Research Summary

Publications

• Li D, Rooney MR, Burmeister LA, Basta NE, Lutsey PL. Trends in daily use of biotin supplements among US adults, 1999-2016. JAMA. 2020;324(6):605–607. doi:10.1001/jama.2020.8144
• Li D, Misialek JR, Jack CR, Mielke MM, Knopman D, Gottesman R, Mosley T, Alonso A. Plasma Metabolites Associated with Brain MRI Measures of Neurodegeneration in Older Adults in the Atherosclerosis Risk in Communities–Neurocognitive Study (ARIC-NCS). Int J Mol Sci 2019;20(7):1744.
• Li D, Hagen C, Fett AR, Bui HH, Knopman D, Vemuri P, Machulda MM, Jack Jr CR, Petersen RC, Mielke MM. Longitudinal association between phosphatidylcholines, neuroimaging measures of Alzheimer's disease pathophysiology, and cognition in the Mayo Clinic Study of Aging. Neurobiol Aging 2019;79:43-9.
• Danni Li, Fangying Huang, Yingchun Zhao, Peter W. Villata, Timothy J. Griffin, Lin Zhang, Ling Li and Fang Yu^. Plasma lipoproteome in Alzheimer’s disease: a proof-of-concept study. Clinical Proteomics2018; 15:31 https://doi.org/10.1186/s12014-018-9207-z
• Danni Li, PhD,  Angela Radulescu, MD, Rupendra T. Shrestha, MD, et al. Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults.  JAMA. 2017;318(12):1150-1160. doi:10.1001/jama.2017.13705

Bio

Dr. Seegmiller is a board certified clinical chemist in the Department's Division of Clinical Chemistry. He focuses his research activities on esoteric testing where he primarily employs mass spectrometry to analyze and develop methods for biological samples in the Advanced Research and Diagnostics Laboratory (ARDL).Before his fellowship and faculty appointment Dr. Seegmiller worked in industry for a mass spectrometry company as a Product Applications Specialist in Clinical Applications. Prior to that he worked in the Department of Laboratory Medicine at Mayo Clinic.

Research Summary

Dr. Seegmiller is an analytical chemist in the Department's Division of Clinical Chemistry.  He focuses his research activities mainly on mass spec analysis of biological samples in the Advanced Research and Diagnostics Laboratory (ARDL).

Publications

Seegmiller JC, Kokaisel EL, Story SJ, Zaun CP, Peters JM, Thomas SN, and Karger AB. Method comparison of SARS-CoV-2 serology assays involving three commercially available platforms and a novel in-house developed enzyme-linked immunosorbent assay Clin Biochem. 2020;S0009-9120(20)30812-2. doi:10.1016/j.clinbiochem.2020.08.004.

Seegmiller JC, Eckfeldt JH, Lieske JC. Challenges in Measuring Glomerular Filtration Rate: A Clinical Laboratory Perspective. Adv Chronic Kidney Dis. 2018 Jan;25(1):84-92. doi: 10.1053/j.ackd.2017.10.006

Seegmiller JC, Miller WG, Bachmann LM. Moving Toward Standardization of Urine Albumin Measurements. EJIFCC. 2017 Dec 19;28(4):258-267. eCollection 2017 Dec.

Schwartz GJ, Wang H, Erway B, Nordin G, Seegmiller J, Lieske JX, Bäck S-E, Miller WG, Eckfeldt JH. Multicenter Laboratory Comparison of Iohexol Measurement. The Journal of Applied Laboratory Medicine Mar 2018, 2 (5) 711-724; DOI: 10.1373/jalm.2017.024240 http://jalm.aaccjnls.org/content/2/5/711

Love SA, Seegmiller JC, Kloss J, Apple FS. Urine Creatinine Concentrations in Drug Monitoring Participants and Hospitalized Patients. J Anal Toxicol. 2016 Sep 1-4.

Larson TS, Seegmiller J, In Reply to 'Iohexol Versus Iothalamate for GFR Measurement'. Am J Kidney Dis. 2016 Jun;67(6):991-2.

Research Summary

Dr. Steffes is a professor and faculty investigator in the Advanced Research and Diagnostics Laboratory (ARDL), which provides central laboratory testing services for large, NIH-funded multi-center clinical trials and studies. Through numerous large-scale longitudinal studies he has earned recognition as a leading researcher in the areas of diabetes mellitus, endocrinology, and cardiovascular disease epidemiology. Steffes is currently principal investigator of the Central Biochemistry Laboratory (CBL) for the Epidemiology of Diabetes Interventions and Complications (EDIC) study, a follow-up to the Diabetes Control and Complications Trial (DCCT) launched in 1984 of which he was also the principal investigator of the CBL. EDIC is a multi-center, longitudinal, observational study designed to use the well-characterized DCCT patient cohort to assess the incidence and predictors of cardiovascular disease events such as heart attack and stroke and diabetic complications related to the eye, kidney, and nerves. In addition, EDIC aims to measure the impact and cost-effectiveness of intensive treatment versus conventional treatment on the quality of life. Steffes is also the principal investigator of the CBL in the GRADE study (Glycemia Reduction Approaches in Diabetes). GRADE is a long-term study with the goal of showing the comparative effectiveness of different treatments for type 2 diabetes, a disease that threatens to become a major public health problem and poses enormous human and economic challenges worldwide.Dr. Steffes is directing central laboratory testing through ARDL for the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study, a multi-center effort exploring the use of novel blood and urine biomarkers to refine the diagnosis and prognosis of patients with acute kidney injury. He is also collaborating with ARDL colleagues to provide central laboratory services for the Coronary Artery Risk Development in Young Adults Study (CARDIA) that examines the development of heart disease in young black and white adults. In addition, he is collaborating in an ongoing effort to standardize the methods to measure hemoglobin A1c (HbA1c), a long-term marker of glycemia. The DCCT/EDIC CBL at the University of Minnesota has defined the measurement of HbA1c in laboratories, both research and clinical. HbA1c is now used to diagnose diabetes mellitus acround the world.

Publications

• de Boer IH, Gao X, Bebu I, Hoofnagle AN, Lachin JM, Paterson A, Perkins BA,  Saenger AK, Steffes MW, Zinman B, Molitch ME. Biomarkers of tubulointerstitial damage and function in type 1 diabetes. BMJ Open Diabetes Res Care. 2017 Nov 14;5(1):e000461.
• de Boer IH, Sun W, Cleary PA, Lachin JM, Molitch ME, Zinman B, Steffes MW; for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group. Longitudinal Changes in Estimated and Measured GFR in Type 1 Diabetes. J Am Soc Nephrol. 2014 Jan 25(4):810-818.
• De Boer, Ian H De; Sun, Wanjie; Gao, Xiaoyu; Cleary, Patricia; Lachin, John M.; Molitch, Mark E.; Steffes, Michael W.; Zinman, Bernard. Effect of intensive diabetes treatment on albuminuria in type 1 diabetes: Long-term follow-up of the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study. The Lancet Diabetes and Endocrinology. 2014 July 2(10):793-800.
• McGee, Paula L.; Steffes, Michael W.; Nowicki, Maren L.; Bayless, Meg L.; Gubitosi-Klug, Rose A.; Cleary, Patricia; Lachin, John M.; Palmer, Jerry P. Insulin secretion measured by stimulated C-peptide in long-established Type 1 diabetes in the Diabetes Control and Complications Trial (DCCT)/ Epidemiology of Diabetes Interventions and Complications (EDIC) cohort: A pilot study. Diabetic Medicine. 2014. June 31(10):1264-1268.

Bio

Dr. Thomas is a clinical chemist and a faculty member of the Advanced Research and Diagnostics Laboratory (ARDL) and a member of the Masonic Cancer Center. She is also the Associate Medical Director of the West Bank Laboratory. Motivated by the growing prevalence of mass spectrometry in the clinical laboratory, Thomas applies discovery and targeted proteomics methods to elucidate the biology of ovarian cancer and analyze proteins derived from alterations in cancer genomes and related biological processes.  Dr. Thomas is a member of the graduate faculty of Molecular Pharmacology and Therapeutics (MPaT); Biochemistry, Molecular Biology, and Biophysics; and Microbiology, Immunology and Cancer Biology (MICaB).

Research Summary

• Mass spectrometry
• Clinical proteomics
• Analytical chemistry

Thomas Research Lab

Publications

PubMed articles list

• Thomas, S.N., French, D., Jannetto, P.J., Rappold, B.A., and Clarke, W. A. Liquid chromatography–tandem mass spectrometry for clinical diagnostics. Nat Rev Methods Primers 2, 96 (2022). https://doi.org/10.1038/s43586-022-00175-x.
• Figueiredo JC, Hirsch FR, Kushi LH,.... Karger AB, Thyagarajan B, Thomas SN, ... Skarbinski J.  Mission, organization, and future direction of the Serological Sciences Network for COVID-19 (SeroNet) epidemiologic cohort studies. Open Forum Infect Dis. 2022 Apr 27;9(6):ofac171. doi: 10.1093/ofid/ofac171.
• Karger AB, Brien JD, Christen JM, Dhakal S, .... Thomas SN, Thyagarajan B, Wajnberg A, Yates JL, Sobhani K. The Serological Sciences Network (SeroNet) for COVID-19: Depth and breadth of serology assays and plans for assay harmonization. mSphere. 2022 Jun 15:e0019322. doi: 10.1128/msphere.00193-22. 
• Chaudhry S, Thomas SN, Simmons GE Jr.Targeting lipid metabolism in the treatment of ovarian cancer.
  Oncotarget. 2022 May 25;13:768-783. doi: 10.18632/oncotarget.28241. eCollection 2022.
• Thomas SN, Karger AB, Altawallbeh G, Nelson KM, Jacobs DR Jr, Gorlin J, Barcelo H, Thyagarajan B. Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity.  Sci Rep. 2022 May 25;12(1):8890. doi: 10.1038/s41598-022-12869-z 
• Ryu J, Thomas SN.  Quantitative mass spectrometry-based proteomics for biomarker development in ovarian cancer.  Molecules. 2021 May 3;26(9):2674. doi: 10.3390/molecules26092674.
• Murthy V, Altawallbeh G, Larson-Nath C, Karger AB, Thomas SN. Transient hyperphosphatasemia following pediatric liver transplantation in a patient with hepatic and skeletal abnormalities.  Clin Chim Acta. 2021 Apr 4:S0009-8981(21)00115-7. doi: 10.1016/j.cca.2021.03.030. 

Research Summary

Dr. Thyagarajan is director of the Division of Molecular Pathology and Genomics and director of the Advanced Research and Diagnostic Laboratory (ARDL). The MDL processes some 25,000 specimens annually related to inherited and infectious diseases, bone marrow engraftment, and blood and solid tumor malignancies.  Thyagarajan and his MDL colleagues are implementing next-generation DNA sequencing (NGS) for diagnosing genetic disease.The MDL has the capacity to test some 5,000 genes implicated in monogenic disorders with the goal of testing all the genes in the human genome (>20,000) and has implemented DNA sequence-based tumor diagnostics.  MDL clinicians have issued hundreds of patient molecular pathology reports based on individual genetic tests and expect that pace of reporting to increase as NGS technology is mainstreamed into clinical medicine. Thyagarajan's team collaborates in this effort with the University of Minnesota Genomics Center, which produces the raw sequence from DNA extracted from clinical samples, and the bioinformatics group at the Minnesota Supercomputing Center, which puts the raw sequence data in a readable format from which clinicians can interpret the diagnostic and prognostic value of genetic variants.At ARDL, Dr. Thyagarajan is principal laboratory investigator for the Hispanic Community Health Study, an NIH-funded multicenter epidemiologic study of Hispanic/Latino populations, and the NIH-funded Long Life Family Study, an international collaborative study of the genetics and familial components of exceptional survival, longevity, and healthy aging. Thyagarajan's personal research program focuses on the role of mitochondria in breast and colorectal cancer.

Publications

• Figueiredo JC, Hirsch FR, Kushi LH, Nembhard WN, Crawford JM, Mantis N, Finster L, Merin NM, Merchant A, Reckamp KL, Melmed GY, Braun J, McGovern D, Parekh S, Corley DA, Zohoori N, Amick BC, Du R, Gregersen PK, Diamond B, Taioli E, Sariol C, Espino A, Weiskopf D, Gifoni A, Brien J, Hanege W, Lipsitch M, Zidar DA, Scheck McAlearney A, Wajnberg A, LaBaer J, Yvonne Lewis E, Binder RA, Moormann AM, Forconi C, Forrester S, Batista J, Schieffelin J, Kim D, Biancon G, VanOudenhove J, Halene S, Fan R, Barouch DH, Alter G, Pinninti S, Boppana SB, Pati SK, Latting M, Karaba AH, Roback J, Sekaly R, Neish A, Brincks AM, Granger DA, Karger AB, Thyagarajan B, Thomas SN, Klein SL, Cox AL, Lucas T, Furr-Holden D, Key K, Jones N, Wrammerr J, Suthar M, Yu Wong S, Bowman NM, Simon V, Richardson LD, McBride R, Krammer F, Rana M, Kennedy J, Boehme K, Forrest C, Granger SW, Heaney CD, Knight Lapinski M, Wallet S, Baric RS, Schifanella L, Lopez M, Fernández S, Kenah E, Panchal AR, Britt WJ, Sanz I, Dhodapkar M, Ahmed R, Bartelt LA, Markmann AJ, Lin JT, Hagan RS, Wolfgang MC, Skarbinski J. Mission, organization, and future direction of the Serological Sciences Network for COVID-19 (SeroNet) epidemiologic cohort studies. Open Forum Infect Dis. 2022 Apr 27;9(6):ofac171. doi: 10.1093/ofid/ofac171.
• Karger AB, Brien JD, Christen JM, Dhakal S, Kemp TJ, Klein SL, Pinto LA, Premkumar L, Roback JD, Binder RA, Boehme KW, Boppana S, Cordon-Cardo C, Crawford JM, Daiss JL, Dupuis AP 2nd, Espino AM, Firpo-Betancourt A, Forconi C, Forrest JC, Girardin RC, Granger DA, Granger SW, Haddad NS, Heaney CD, Hunt DT, Kennedy JL, King CL, Krammer F, Kruczynski K, LaBaer J, Lee FE, Lee WT, Liu SL, Lozanski G, Lucas T, Mendu DR, Moormann AM, Murugan V, Okoye NC, Pantoja P, Payne AF, Park J, Pinninti S, Pinto AK, Pisanic N, Qiu J, Sariol CA, Simon V, Song L, Steffen TL, Stone ET, Styer LM, Suthar MS, Thomas SN, Thyagarajan B, Wajnberg A, Yates JL, Sobhani K. The Serological Sciences Network (SeroNet) for COVID-19: Depth and breadth of serology assays and plans for assay harmonization. mSphere. 2022 Jun 15:e0019322. doi: 10.1128/msphere.00193-22.
• Thomas SN, Karger AB, Altawallbeh G, Nelson KM, Jacobs DR Jr, Gorlin J, Barcelo H, Thyagarajan B. Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity.  Sci Rep. 2022 May 25;12(1):8890. doi: 10.1038/s41598-022-12869-z. 
• Mroz P, Michel S, Allen JD, Meyer T, McGonagle EJ, Carpentier R, Vecchia A, Schlichte A, Bishop JR, Dunnenberger HM, Yohe S, Thyagarajan B, Jacobson PA, Johnson SG. Development and implementation of in-house pharmacogenomic testing program at a major academic health system. Front Genet. 2021 Oct 20;12:712602. doi: 10.3389/fgene.2021.712602.
• Martinez RJ, Pankratz N, Schomaker M, Daniel J, Beckman K, Karger AB, Thyagarajan B, Ferreri P, Yohe SL, Nelson AC. Prediction of false positive SARS-CoV-2 molecular results in a high-throughput open platform system. J Mol Diagn. 2021 Jun 8:S1525-1578(21)00166-5. doi: 10.1016/j.jmoldx.2021.05.015
• Ryan J. Martinez, Qing Kang, Davis Nennig, Nathanael G. Bailey, Noah A. Brown, Bryan L. Betz, Muneesh Tewari, Bharat Thyagarajan, Veronika Bachanova, Pawel Mroz. One-Step Multiplexed Droplet Digital Polymerase Chain Reaction for Quantification of p190 BCR-ABL1 Fusion Transcript in B-Lymphoblastic Leukemia.  Arch Pathol Lab Med2021; doi:https://doi.org/10.5858/arpa.2020-0454-OA
• Thomas SN, Altawallbeh G, Zaun CP, Pape KA, Peters JM, Titcombe PJ, Dileepan T, Rapp MJ, Bold TD, Schacker TW, Arbefeville S, Ferrieri P, Thyagarajan B, Jenkins MK, Karger AB. Initial determination of COVID-19 seroprevalence among outpatients and healthcare workers in Minnesota using a novel SARS-CoV-2 total antibody ELISA. Clin Biochem. 2021 Feb 1:S0009-9120(21)00027-8. doi: 10.1016/j.clinbiochem.2021.01.010

Research Summary

Dr. Tsai is a member of the Division of Molecular Pathology and Genomics who studies genetic and phenotypic biomarkers for cardiovascular diseases (CVD) risk assessment. He has been the director of central laboratories for many large population studies including the Multi-Ethnic Study of Atherosclerosis (MESA), Genetics of Lipid Lowering Drugs and Diet Network (GOLDN), and is a faculty investigator in the Advanced Research and Diagnostics Laboratory (ARDL).Tsai was among the first to recognize the importance of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle heterogeneities, the inverse association of serum triglyceride with particle sizes of lipoproteins, and the implication of these phenomena in assessing CVD risk. His laboratory continues to be active in this area and he continues to publish research findings on the utility of non-traditional lipoprotein measurements for CVD risk prediction. Beyond lipids, Dr Tsai has extensively studied other risk factors. For example, Tsai helped pioneer the study of genetic and nutritional influence on serum homocysteine level and the usefulness of serum homocysteine levels in the risk prediction of venous thrombosis and coronary artery diseases.Tsai's laboratory is among the first to acquire the capability to analyze serum and red blood cell membrane phospholipid fatty acid composition. Currently, the Tsai laboratory remains one of the nation's most active in investigating fatty acids and heart disease risk, having performed studies in large population-based cohorts including besides MESA and GOLDN the Coronary Artery Risk Development in Young Adults Study (CARDIA), the Women's Health Study, and the Physicians' Health Study. His team has been researching the role of omega-3 and omega-6 fatty acids in human health. A lower ratio of omega-6/omega-3 fatty acids may help reduce the risk of many inflammation-related chronic diseases such as obesity, type 2 diabetes, and heart disease that are prevalent in Western societies and developing countries.Dr. Tsai's laboratory has recently moved into NIH-funded large-scale phenotypic and genotypic biomarker studies to investigate risk factors related to CVD such as hypertension and diabetes in pregnant women. These conditions are typically transient but can lead to complicated pregnancies and post-natal development of chronic disease, as well as predisposing women to the development of diabetes and hypertension. Through his continuing partnership with NIH and the National Institute of Child Health Care and Development, (NICHD), Dr. Tsai hopes to contribute to a more thorough understanding of the mechanisms behind these poorly studied conditions.Since 2009, Dr. Tsai's laboratory also conducted a long term collaboration with the Division of Intramural Population Health Research in the National Institute of Child Health Care and Development (NICHD) studying hypertension and diabetes in pregnant women as well as infertility and birth defects.More than 50 projects have been funded by NIH/NICHD for this collaboration over the past 11 years using both phenotypic and genotypic approaches including omics platforms such as metabolomics, microbiomes, DNA methylation/epigenetics, and next generation DNA and RNA sequencing. Through his continuing partnership with NIH and NICHD, Dr. Tsai hopes that this long-term collaboration will result in significant contributions to these important but relatively understudied diseases.

Publications

• Garg PK, Guan W, Nomura S, Weir NL, Karger AB, Duprez D, Tsai MY. Associations of plasma omega-3 and omega-6 pufa levels with arterial elasticity: the multi-ethnic study of atherosclerosis. Eur J Clin Nutr. 2022 Jun 
• Karger AB, Steffen BT, Nomura SO, Guan W, Garg PK, Szklo M, Budoff MJ, and Tsai MY. Association between homocysteine and vascular calcification incidence, prevalence, and progression in the MESA cohort. J Am Heart Assoc. 2020 Feb 4;9(3):e013934. doi: 10.1161/JAHA.119.013934. Epub 2020 Jan 30.
• Weir NL, Nomura SO, Steffen BT, Guan W, Karger AB, Klein R, Klein BEK, Cotch MF, and Tsai MY. Associations between omega-6 polyunsaturated fatty acids, hyperinsulinemia and incident diabetes by race/ethnicity: The Multi-Ethnic Study of Atherosclerosis. Clin Nutr. 2020 Jan 22. pii: S0261-5614(20)30008-X. doi: 10.1016/j.clnu.2020.01.003.
• Cao J, Nomura SO, Steffen BT, Guan W, Remaley AT, Karger AB, Ouyang P, Michos ED, and Tsai MY. Apolipoprotein B discordance with low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in relation to coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).J Clin Lipidol. 2019 Nov 29. pii: S1933-2874(19)30354-X. doi: 10.1016/j.jacl.2019.11.005.
• Steffen BT, Bielinski SJ, Decker PA, Berardi C, Larson NB, Pankow JS, Michos ED, Hanson NQ, Herrington DM, Tsai MY. Low high-density lipoprotein cholesterol and particle concentrations are associated with greater levels of endothelial activation markers in Multi-Ethnic Study of Atherosclerosis participants. J Clin Lipidol. 2017 Jun 13. pii: S1933-2874(17)30347-1. doi: 10.1016/j.jacl.2017.05.018.