Pamala Jacobson, PharmD, FCCP

Distinguished Professor, Department of Experimental and Clinical Pharmacology (ECP)

Pamala Jacobson

Contact Info

Mailing Address:
University of Minnesota
College of Pharmacy
Department of Experimental and Clinical Pharmacology
7-115 Weaver-Densford Hall
308 Harvard St. SE
Minneapolis, MN 55455

Distinguished Professor, Department of Experimental and Clinical Pharmacology (ECP)

Professor of Medicine (Joint Appointment), Division of Hematology, Oncology and Transplantation

Director of the Pharmacogenomics U of M Alliance (PUMA-IPM) Institute of Personalized Medicine, Department of Experimental and Clinical Pharmacology (ECP)


Residency, University of Michigan

Specialty Residency, Infections Disease University of Michigan

PharmD, University of Nebraska

Research

Research Summary/Interests

Research Interests

  • Concentration and dose response relationships
  • Pharmacokinetics
  • Pharmacogenetics
  • Pharmacodynamics
  • Immunosuppressants
  • Anticancer agents
  • Stem cell transplantation and organ transplant
  • Oncology
  • Pharmacogenomics in health disparities

Research Projects

Pharmacokinetics, pharmacodynamics and pharmacogenetics of immunosuppressants and anticancer agents.  Clinical pharmacology of fludarabine, cyclophosphamide, doxorubicin, mycophenolate, cyclosporine, tacrolimus.

Publications

PubMed

Rozemarijn Snoek, Jessica van Setten, Brendan J. Keating, Ajay K. Israni, Pamala A. Jacobson, William S. Oetting, Arthur J. Matas, Rosalyn B. Mannon, Zhongyang Zhang, Weijia Zhang PhD, Ke Hao, Barbara Murphy, Roman Reindl-Schwaighofer, Andreas Heinzl, Rainer Oberbauer, Ondrej Viklicky, Caragh Stapleton, Stephan J.L. Bakker, Harold Snieder, Edith D.J. Peters, Bert van der Zwaag, Nine V.A.M. Knoers, Martin H. de Borst, Albertien M. van Eerde. NPHP1 Gene Deletions Cause Adult Onset End Stage Renal Disease. Journal American Society of Nephrology. 2018 Accepted.

Okour M, Jacobson PA, Ahmed MA, Israni AK, Brundage RC. Mycophenolic acid (MPA) and its metabolites in kidney transplant recipients: a semi-mechanistic enterohepatic circulation model to improve estimating exposure. J Clin Pharmacology, 2018 Jan 12. doi: 10.1002/jcph.1064. [Epub ahead of print] [NIHMSID 922517]

Casey R. Dorr, William S. Oetting, Pamala A. Jacobson, Ajay K. Israni. Genetics of Acute Rejection after Kidney Transplantation. Transplant Int. 2017 doi: 10.1111/tri.13084. [Epub ahead of print 8 November 2017] Paper featured in Top News in the Society for Transplant Surgeons Newsletter.

William S. Oetting, Casey Dorr, Rory P. Remmel, Arthur J. Matas, Ajay K. Israni, Pamala A. Jacobson. Concepts of Genomics in Kidney Transplantation (Review). Curr Transplant Rep. Jun;2(4):116-123. doi: 10.1007/s40472-017-0153-x.

Yanik MV, Irvin R, Beasley, TM, Jacobson PA, Julian, BA. Limdi, NA. Influence of kidney transplant status on warfarin dose, anticoagulation control, and risk of hemorrhage. Pharmacotherapy, 2017, Nov:37(11):1366-1373. doi: 10.1002/phar.2032. Epub 2017 Nov 2. [PMID 28949423]

Dorr CR*, Remmel RP, Muthusamy A, Fisher J, Moriarity B, Yasuda K, Wu B, Guan W, Schuetz EG, Oetting WS, Jacobson PA, Israni PA. CRISPR/Cas9 genetic modification of CYP3A5 *3 in HuH-7 human hepatocyte cell line leads to cell lines with increased midazolam and tacrolimus metabolism. Drug Metabolism and Disposition, August 2017, 45 (8) 957-965. DOI: https://doi.org/10.1124/dmd.117.076307. Received Gillette award for best paper of the year.

Oetting WA, Jacobson PA, Israni AK. Editorial: Validation is critical for genome wide association study based associations. Am J Transplant. 2017:17(2):318-319. [PMID 27640398]

Wasko J, Westholder JS, Jacobson PA. Rifampin-sirolimus-voriconazole interaction in a hematopoietic cell transplant recipient. J Oncol Pharm Pract. 2017 Jan;23(1):75-79.[PMID: 2676300]

Bejanyan N, Rogosheske J, DeFor TE, Lazaryan A, Arora M, Holtan SG, Jacobson PA, MacMillan ML, Verneris MR, Blazar BR, Weisdorf DJ, Wagner JE, Brunstein CG. Sirolimus and Mycophenolate Mofetil as Calcineurin Inhibitor-Free GVHD Prophylaxis for Reduced Intensity Umbilical Cord Blood Transplantation. Biol Blood and Marrow Transplant. 2016 Nov;22(11):2025-2030 [PMID:27519278]

Liang S*, Brundage RC, Jacobson PA, Blaes, A, Kirstein, MN. Pharmacokinetic-pharmacodynamic modeling of acute N-terminal pro B-type natriuretic peptide after doxorubicin infusion in breast cancer. Br J Clin Pharmacol. (2016) 82, 773–783. [PMID 27128712]

Sanghavi K*, Wiseman A*, Kirstein M, Cao Q, Brundage R, Jensen K, Rosgosheske J, Kurtzweil A, Long-Boyle J, Wagner J, Warlick E, Brunstein CG, Weisdorf D, Jacobson PA. Personalized Fludarabine Dosing To Reduce Non-Relapse Mortality In Hematopoietic Stem Cell Transplant Recipients Receiving Reduced Intensity Conditioning. Transl Research. 2016 Sep;175:103-115. [PMID 27094990]

Oetting WS, Schladt DP, Guan W, Miller MB, Remmel RP, Dorr C*, Sanghavi K*, Mannon RB, Herrera B, Matas AJ, Salomon DR, Kwok PY, Keating BJ, Israni AK, Jacobson PA for the DeKAF Investigators. Genome wide association study of tacrolimus concentrations in African American kidney transplant recipients identifies multiple CYP3A5 alleles. Am J Transplant 2016 Feb;16(2):574-82. [PMID 26485092]

Sanghavi K*, Brundage RC, Miller MB, Schladt DP, Israni AK, Guan W, Oetting WS, Mannon RB, Remmel RP, Matas AJ, Jacobson PA. Genotype-guided tacrolimus dosing in African American kidney transplant recipients. The Pharmacogenomics Journal. 2015, 1–8 [PMID: 26667830]

International Genetics & Translational Research in Transplantation Network (iGeneTRAiN). Keating BJ, van Setten J, Jacobson PA, Holmes MV, Verma SS, Chandrupatla HR, Nair N, Gao H, Li YR, Chang B-L, Wong C, Phillips R, Cole BS, Mukhtar E, Zhang W, Cao H, Mohebnasab M, Hou C, Lee T, Steel L, Shaked O, Garifallou J, Miller MB, Karczewski KJ, Akdere A, Gonzalez A, Lloyd KM, McGinn D, Michaud Z, Colasacco A, Lek M, Fu Y, Pawashe M, Guettouche T, Himes A, Perez L, Guan W, Wu B, Schladt D, Menon M, Zhang Z, Tragante V, de Jonge N, Otten HG, de Weger RA, van de Graaf EA, Baan CC, Olivier C. Manintveld OC, De Vlaminck I, Piening BD, Strehl C, Shaw M, Snieder H, Klintmalm GB, O'Leary JG, Amaral S, Goldfarb S, Rand E, Rossano JW, Kohli U¸ Heeger P, Stahl E, Christie JD, Hernandez Fuentes M, Levine JE, Aplenc R, Schadt EE, Stranger BE, Kluin J, Potena L, Zuckermann A, Khush K, Alzahrani AJ, Al-Muhanna FA, Amein K. Al-Ali, Al-Al R, Al-Rubaish AM, Al-Mueilo S, Byrne EM, Miller D, Alexander SI, Onengut-Gumuscu S, Rich SS, Suthanthiran M, Tedesco H, Saw CL, Ragoussis J, Kfoury AG, Horne B, Carlquist J, Mark B. Gerstein MB, Reindl-Schwaighofer R, Oberbauer R, Wijmenga C, Palmer S, Pereira AC, Segovia J, Alonso-Pulpon LA, Comez-Buen M, Vilches C, Jaramillo N, de Borst MH, Naesens M, Hao K, MacArthur DG, Balasubramanian S, Conlon PJ, Lord GM, Ritchie MG, PhD, Snyder M, Olthoff KM, Moore JH, Petersdorf EW, Kamoun M, Wang J, Monos DS, de Bakker PIW, Hakonarson H, Murphy B, Lankree MB, Garcia-Pavi P, Oetting WS, Birdwell KA, Bakker SJL, Israni AK, Shaked A, Asselbergs FW. Design and implementation of the International Genetics & Translational Research in Transplantation Network (iGeneTRAiN). Transplantation 2015; 99:2401-2412. [PMID: 26479416]

Li YR, van Setten J, Verma SS, Lu Y, Holmes MV, Gao H, Lek M, Nair N, Chandrupatla H, Chang B, Karczewski KJ, Wong C, Mohebnasab M, Mukhtar E, Phillips R, Tragante V, Hou C, Steel L, Lee T, Garifallou J, Guettouche T, Cao H, Guan W, Himes A, van Houten J, Pasquier A, Yu R, Carrigan E, Miller MB, Schladt D, Akdere A, Gonzalez A, Llyod KM, McGinn D, Gangasani A, Michaud Z, Colasacco A, Snyder J, Thomas K, Wang T, Wu B, Alzahrani AJ, Al-Ali AK, Al-Muhanna FA, Al-Rubaish AM, Al-Mueilo S, Monos DS, Murphy B, Olthoff KM, Wijmenga C, Webster T, Kamoun M, Balasubramanian S, Lanktree MB, Oetting WS, Garcia-Pavia P, MacArthur DG, de Bakker PI, Hakonarson H, Birdwell KA, Jacobson PA, Ritchie MD, Asselbergs FW, Israni AK, Shaked A, Keating BJ. Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies. Genome Medicine 2015, 7:90. [PMID: 26423053]

Pulk R*, Schladt D, Weihau, G, Oetting W, Israni A, Matas A, Jacobson PA. Multi-Gene Pharmacogenomics of Tacrolimus Troughs in Kidney Transplant Recipients. Pharmacogenomics 2015; 16: 841-854. [PMID: 26067485]

Dorr C*, Wu B, Guan W; Muthusamy A, Sanghavi K*, Schladt DP, Maltzman JS, Scherer SE, Brott MJ, Matas AJ, Jacobson PA, Oetting WS, Israni AK. Differentially expressed gene transcripts using RNA sequencing from the blood of immunosuppressed kidney allograft recipients. PLoS One 2015: 10:e0125045. [PMID 25946140]

Bejanyan N, Rogosheske J, DeFor T, Lazaryan A, Esbaum K, Holtan S, Arora M, MacMillan ML, Weisdorf D, Jacobson P, Wagner J, Brunstein CG. Higher dose of mycophenolate mofetil reduces acute graft-versus-host disease in reduced-intensity conditioning double umbilical cord blood transplantation. Biol Blood

Marrow Transplant. 2015 May;21(5):926-33. (PMID: 25655791)
Blaes A, Duprez D, Defor T, Shanley R, Beckwith H, Haddad T, Potter D, Yee D, Sanghavi K*, Jacobson P. Angiotensin Converting Enzyme Inhibitors (ACEI) and doxorubicin pharmacokinetics in women receiving adjuvant breast cancer treatment. Springerplus. 2015 Jan 23;4:32. (PMID:2564615)

McCune JS, Jacobson P, Wiseman A*, Militano O. Optimizing drug therapy in pediatric SCT: focus on pharmacokinetics. Bone Marrow Transplant. 2015 Feb;50(2):165-72. Epub 2014 Oct 27. (PMID 2537008).

Oetting WS, Guan, W, Schladt DP, Wildebush WA, Becker J, Thyagarajan B, Jacobson PA, Matas AJ, Israni AK. Telomere length of recipients and living kidney donors and chronic graft dysfunction in kidney transplants. Transplantation. 2014 Feb 15;97(3):325-9. [PMID:24492422]

Oetting WS, Jacobson PA, Israni AK. Editorial ; Transplant rejection and risk: in search of the genetic dark matter. J Gastrointestin Liver Dis. 2013 Jun;22(2):125-6 (PMID:23799208, PMCID: PMC4105001)

Israni AK, Riad SM, Leduc R, Oetting WS, Guan W, Schladt D, Matas AJ, Jacobson PA; DeKAF Investigators. Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: a lesson learned from DeKAF Genomics. Transpl Int. 2013 Oct;26(10):982-9. (PMID: 23879408, PMCID: PMC3787982)

Israni AK, Leduc R, Jacobson PA, Wildebush W, Guan W, Schladt D, Matas AJ, Oetting WS; for the DeKAF Investigators. Inflammation in the setting of chronic allograft dysfunction post-kidney transplant: phenotype & genotype. Clin Transplant 2013 May-June 27(3):348-58 (PMID: 23350966, PMCID: PMC3647022)

Thyagarajan B, Jackson S, Basu S, Jacobson P, Gross MD, Weisdorf DJ, Arora M. Association between genetic variants in adhesion molecules and outcomes after hematopoietic cell transplantation. Int J Immunogenet. 2013 Apr;40(2):108-15 (PMID: 22646485, PMCID: PMC3458148)

Frymoyer A, Verotta D, Jacobson P, Long-Boyle J. Population pharmacokinetics of unbound mycophenolic acid in adult allogeneic hematopoietic cell transplantation: effect of pharmacogenetic factors. Br J Clin Pharmacol. 2013 Feb;75; (2):463-75. (PMID:22765258, PMCID: PMC3579261)

Oetting WS, Guan W, Schladt DP, Leduc RE, Jacobson PA, Matas AJ, Chinnakotla S, Schröppel B, Murphy BT, Israni AK. Donor polymorphisms of toll-like receptor 4 associated with graft failure in liver transplant recipients. Liver Transpl. 2012 Dec;18(12):1399-405. (PMID:22987288, PMCID: PMC3518641)
Jacobson PA, Schladt D, Oetting WS, Leduc R, Guan W, Matas AJ, Israni A. DeKAF Investigators. Lower Calcineurin Inhibitor Doses in Older Compared to Younger Kidney Transplant Recipients Yield Similar Troughs. Am J Transplant. 2012 Dec;12(12):3326-36. (PMID:22947444)

Johnson LA, Tretyakova N, Jacobson PA. Obesity effects on cyclophosphamide-induced DNA damage in hematopoietic cell transplant recipients. In Vivo. 2012 Sep;26(5):853-7. (PMID:22949601)

Abecassis M, Bridges ND, Clancy CJ, Dew MA, Eldadah B, Englesbe MJ, Flessner MF, Frank JC, Friedewald J, Gill J, Gries C, Halter JB, Hartmann EL, Hazzard WR, Horne FM, Hosenpud J, Jacobson P, Kasiske BL, Lake J, Loomba R, Malani PN, Moore TM, Murray A, Nguyen MH, Powe NR, Reese PP, Reynolds H, Samaniego MD, Schmader KE, Segev DL, Shah AS, Singer LG, Sosa JA, Stewart ZA, Tan JC, Williams WW, Zaas DW, High KP. Workshop Proceedings. Solid Organ Transplantation in Older Adults: Current Status and Future Research. Summarized the Workshop held on January 23-24, 2012. Am J Transplant. 2012 Oct;12(10):2608-22. (PMID:22958872, PMCID:PMC3459231).

Passey C*, Birnbaum AK, Brundage RC, Oetting WS, Leduc RE, Israni AK, Guan W, Matas AJ, Jacobson PA. Validation of tacrolimus equation to predict troughs using genetic and clinical factors. Pharmacogenomics. 2012 Jul;13(10):1141-7. (PMID:22909204, PMCID: PMC3579500)

Kim H*, Long-Boyle J*, Rydholm N, Orchard PJ, Tolar J, Smith AR, Jacobson P, Brundage R. Population pharmacokinetics of unbound mycophenolic acid in pediatric and young adult patients undergoing allogeneic hematopoietic cell transplantation. J Clin Pharmacol. 2012 Nov;52(11);1665-1675. (PMID:22110162)
Jensen K*, Johnson LA, Jacobson PA, Kachler S, Kirstein MN, Lamba J, Klotz KN. Cytotoxic purine nucleoside analogues bind to A1, A2A, and A3 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol. 2012 May;385(5):519-25. (PMID: 22249336, PMCID: PMC3831620)

Jacobson PA, Schladt D, Israni A, Oetting WS, Lin Y*, Leduc R, Guan W, Lamba V, Matas AJ; DeKAF Investigators. Genetic and clinical determinants of early, acute calcineurin inhibitor-related nephrotoxicity: results from a kidney transplant consortium. Transplantation. 2012 Mar 27;93(6):624-31. (PMID: 22334041, PMCID: PMC3299910, NIHMSID: NIHMS349278)

Johnson LA, Malayappan B, Tretyakova N, Campbell C, MacMillan ML, Wagner JE, Jacobson PA. Formation of cyclophosphamide specific DNA adducts in hematological diseases. Pediatr Blood Cancer. 2012 May;58(5):708-14. (PMID: 21793181, PMCID: PMC3204332, NIHMSID: NIHMS301541)

Jacobson PA, Schladt D, Leduc R, Guan W, Matas AJ, Lamba V, Mannon RB, Julian BA, Israni A; for the DEKAF investigators. Reply to "genetic determinants of mycophenolate-related anemia and leukopenia after transplantation. Transplantation. 2012 Mar 27;93(6):624-31.

Oetting WS, Schladt DP, Leduc RE, Jacobson PA, Guan W, Matas AJ, Israni A; DeKAF Investigators. Validation of single nucleotide polymorphisms associated with acute rejection in kidney transplant recipients using a large multi-center cohort. Transpl Int. 2011 Dec;24(12):1231-8. (PMID: 21955043, PMCID: PMC3208796, NIHMSID: NIHMS323689)

Passey C*, Birnbaum AK, Brundage RC, Oetting WS, Jacobson PA. Dosing equation for tacrolimus using genetic variants and clinical factors. Br J Clin Pharmacol. 2011 Dec; 72(6):948-957. (PMID: 21671989, PMCID: PMC3244642)

Jacobson PA, Schladt D, Leduc R, Guan W, Matas AJ, Lamba V, Mannon RB, Julian BA, Israni A; for the DEKAF investigators. Genetic determinants of mycophenolate-related anemia and leukopenia after transplantation. Transplantation. 2011 Feb 15; 91(3):309-316. (PMID: 21107304, PMC 3711617)

Jacobson PA, Oetting WS, Brearley AM, Leduc R, Guan W, Schladt D, Matas AJ, Lamba V, Julian BA, Manon RB, Israni A; DEKAF investigators. Novel polymorphisms associated with tacrolimus trough concentrations: results from a multicenter kidney transplant consortium. Transplantation. 2011 Feb 15; 91(3):300-308. (PMID: 21206424, PMC 3579501)

Long-Boyle J*, Huang J*, Rydholm N, Smith A, Orchard P, Tolar J, Jacobson P. Pharmacokinetics of clofarabine in patients with high risk inherited metabolic disorders undergoing brain-sparing hematopoietic cell transplantation. J Clinical Pharmacol. 2011 May;51(5):679-8. (PMID: 20525919)

Israni A, Leduc R, Holmes J, Jacobson PA, Guan W, Schladt D, J Chen, Matas AJ, Oetting WS. Single-nucleotide polymorphisms, acute rejection and severity of tubulitis in kidney transplantation, accounting for center-to-center variation. Transplantation. 2010 Dec 27; 90(12):1401-1408. (PMID: 21085059, PMC 3594840)

Malayappan B*, Johnson L, Nie B, Panchal D, Matter B, Jacobson P, Tretyakova N. Quantitative high-performance liquid chromatography-electrospray ionization tandem mass spectrometry analysis of bis-N7-guanine DNA-DNA cross-links in white blood cells of cancer patients receiving cyclophosphamide therapy. Anal Chem. 2010 May 1;82(9):3650-8. (PMID: 20361772)

Long-Boyle JR*, Green K*, Brunstein CG, Cao Q, Rogosheske J, Weisdorf DJ, Miller JS, Wagner JE, McGlave PB, Jacobson PA. High fludarabine exposure is associated with increased treatment-related mortality after nonmyeloablative hematopoietic cell transplantation. Bone Marrow Transplant. 2011 Jan;46(1):20-6. (PMID: 20383215, PMCID: PMC2904846, NIHMSID: NIHMS175700)

Jacobson PA, Huang J, Wu J, Kim M, Logan B, Alousi A, Grimley M, Bolaños-Meade J, Ho V, Levine J, Weisdorf D. Mycophenolate Pharmacokinetics and Association with Response to Acute Graft vs Host Disease (GVHD) Treatment From the Blood and Marrow Transplant Clinical Trials Network. Biol Blood Marrow Transplant. 2010 Mar;16(3):421-429. (PMID: 19925875, PMCID: PMC3104501, NIHMSID: NIHMS160263)

Martin PJ, Storer BE, Rowley SD, Flowers ME, Lee SJ, Carpenter PA, Wingard JR, Shaughnessy P, DeVetten MP, Jagasia M, Fay JW, van Besien K, Gupta V, Kitco C, Jacobson PA, Weisdorf D. Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease. Blood 2009:113:21: 5074-82. (PMID: 19270260, PMCID: PMC2686178)

Jacobson PA, Farag El-Massah S*, Rogosheske J, Kerr A, Boyle-Long J*, DeFor T, Jennisen C, Brunstein C, Wagner J, Tomblyn M, Weisdorf D. Comparison of Two Mycophenolate Mofetil Dosing Regimens Following Hematopoietic Cell Transplantation. Bone Marrow Transplantation, 2009; 44,113-120. (PMID: 19151792, PMCID: PMC3204943, NIHMSID: NIHMS326007)

Johnson LA, Oetting WS, Basu S, Prausa S*, Matas A, Jacobson PA. Pharmacogenetic effect of the UGT polymorphisms on mycophenolate is modified by calcineurin inhibitors. Eur J Clin Pharmacol. 2008;64;1047-56 (PMID: 18568343)

Ibrahim RB, Abidi MH, Ayash LJ, Cronin SM, Mulawa J, Jacobson PA, Smith DW, Uberti JP, Edwards DJ. Effect of aprepitant on intravenous tacrolimus disposition in reduced intensity hematopoietic cell transplantation. J Oncol Pharm Pract. 2008;14:113-121. (PMID: 18556719)

Johnson L*, Orchard P, Baker KS, Brundage R, Cao Q, Wang X, Langer E, Farag-El Maasah S*, Ross JA, Remmel RP, Jacobson PA. Glutathione-s-transferase A1 Genetic Variants Reduce Busulfan Clearance in Children Undergoing Hematopoietic Cell Transplantation. J Clin Pharmacology. 2008. 48 1052-1062. (PMID: 18635758, PMCID: PMC3204946, NIHMSID: NIHMS326005)

Jacobson P, Huang J*, Rydholm N, Tran M*, DeFor T, Tolar J, Orchard PJ. Higher mycophenolate dose requirement in children undergoing hematopoietic cell transplantation (HCT). J Clin Pharmacol. 2008:48;485-494. (PMID: 18296555)

Kirstein MN, Root SA, Moore MM, Wieman KM, Williams BW, Jacobson PA, Marker PH, Tuttle TM. Exposure-response relationships for oxaliplatin treated colon cancer cells, Anticancer Drugs. 2008:19(1):37-44. (PMID: 18043128)