Maryam Afkarian, MD-PhD

Maryam Afkarian

Position Title
Associate Professor

Unit
Department of Internal Medicine (Nephrology), School of Medicine

5317 GBSF Building
Bio

Research Interests

Using mass spectrometry to understand pathophysiology of diabetic kidney disease

More than 10% of people in the US (and the world) have diabetes. Close to 40% have prediabetes. The high blood sugar in both diabetes and prediabetes causes damage to many organs, including the kidneys, the heart, blood vessels, nervous system, etc. 30-40% of people with diabetes develop kidney disease (diabetic kidney disease, DKD) and end up on dialysis. More importantly, those who escape from kidney disease can live as long as people without diabetes. Diabetes begins to damage the kidneys almost from beginning of its onset, but we currently can only diagnose it 10-20 years after it has started. In addition, our current treatments (controlling blood pressure and blood sugar and use of renin-angiotensin inhibitors, only slows DKD progression but does not stop it and cannot reverse it. Extensive work in cells and animal models has produced a wealth of data about the pathways that may be involved in DKD pathogenesis. My work is focused on translating that information to human disease. To do that, I use mass spectrometry to quantify the protein components of the pathways involved in animal models of DKD in samples from humans with DKD (urine, blood and kidney tissue). Analyzing that information using biostatistics and epidemiologic tools, we can determine if these pathways play a role in human DKD as well. Using this approach, we were the first group to publish evidence that implicated the complement pathway in DKD pathogenesis, paving the way for intervening in this pathway as a more effective treatment of advanced DKD.

Dietary interventions to reduce obesity and diabetes

It isn't just your imagination. Obesity rates are skyrocketing: In 1960s, 13% of US adults were obese (defined as those with a body mass index of 30 or more); in 2015-2016, this rose to 40%. By 2030, we're projected to have 50% obesity. This tsunami is not just cosmetic. It brings with it a concomitant rise in prediabetes and diabetes, both of them causing significant chronic damage to many vital organs. We're already seeing a rise in heart failure in lock step with rise in prediabetes, and diabetes alone is currently the leading cause of kidney disease, kidney failure requiring dialysis, limb amputations and blindness. This is all preventable. There is abundant data showing us how a modification of our diet and lifestyle can add meaningful and healthy years to our lives.  While the science of nutrition certainly has its fair share of controversy, there's a great deal of consensus and understanding. Focusing on this consensus and understanding, we have proposed a clinical trial to use continuous glucose monitoring (example below) to find out how each person's blood sugar changes in response to different foods. This allows us to individually tailor the diet to each study participant with obesity and diabetes or prediabetes to help them lose weight and also reduce blood sugar, without sacrificing quality of life.

 

Figure

Grad Group Affiliations

  • Biochemistry, Molecular, Cellular and Developmental Biology
  • Nutrition (pending)

Specialties / Focus

  • Genomics, Proteomics and Metabolomics

Courses

  • TBD

Honors and Awards

1993                   HHMI Undergraduate Research Scholarship, UC Berkeley

1994                   Phi Beta Kappa, UC Berkeley

1994                   Summa cum laude, UC Berkeley

1994                   Dean’s Honor list, UC Berkeley

1994                   Outstanding Undergraduate Immunology Research, UC Berkeley

1995-2003          Medical Scientist Training Program, Washington University, St Louis

1995-1999          Olin Fellowship for Women, Washington University, St Louis

1998                   Distinguished Teaching Assistant Award, Washington University

2008-2010          Scholars in Clinical Sciences Program, Harvard Medical School

Professional Societies

  • American Society of Nephrology

Degrees

  • MD-PhD (immunology, 1995-2003)
  • MS (medical sciences, 2006)

Publications


1: Garrett-Bakelman FE, Darshi M, Green SJ, Gur RC, Lin L, Macias BR, McKenna MJ,
Meydan C, Mishra T, Nasrini J, Piening BD, Rizzardi LF, Sharma K, Siamwala JH,
Taylor L, Vitaterna MH, Afkarian M, Afshinnekoo E, Ahadi S, Ambati A, Arya M,
Bezdan D, Callahan CM, Chen S, Choi AMK, Chlipala GE, Contrepois K, Covington M,
Crucian BE, De Vivo I, Dinges DF, Ebert DJ, Feinberg JI, Gandara JA, George KA,
Goutsias J, Grills GS, Hargens AR, Heer M, Hillary RP, Hoofnagle AN, Hook VYH,
Jenkinson G, Jiang P, Keshavarzian A, Laurie SS, Lee-McMullen B, Lumpkins SB,
MacKay M, Maienschein-Cline MG, Melnick AM, Moore TM, Nakahira K, Patel HH,
Pietrzyk R, Rao V, Saito R, Salins DN, Schilling JM, Sears DD, Sheridan CK,
Stenger MB, Tryggvadottir R, Urban AE, Vaisar T, Van Espen B, Zhang J, Ziegler
MG, Zwart SR, Charles JB, Kundrot CE, Scott GBI, Bailey SM, Basner M, Feinberg
AP, Lee SMC, Mason CE, Mignot E, Rana BK, Smith SM, Snyder MP, Turek FW. The NASA
Twins Study: A multidimensional analysis of a year-long human spaceflight.
Science. 2019 Apr 12;364(6436). pii: eaau8650. doi: 10.1126/science.aau8650.
PubMed PMID: 30975860.


2: Vaisar T, Durbin-Johnson B, Whitlock K, Babenko I, Mehrotra R, Rocke DM,
Afkarian M. Erratum. Urine Complement Proteins and the Risk of Kidney Disease
Progression and Mortality in Type 2 Diabetes. Diabetes Care 2018;41:2361-2369.
Diabetes Care. 2019 Apr 1. pii: dc19er06a. doi: 10.2337/dc19-er06a. [Epub ahead
of print] PubMed PMID: 30936112.


3: Kahkoska AR, Isom S, Divers J, Mayer-Davis EJ, Dolan L, Shah AS, Afkarian M,
Pettitt DJ, Lawrence JM, Marcovina S, Saydah SH, Dabelea D, Maahs DM, Mottl AK;
SEARCH for Diabetes in Youth Study Group. The early natural history of
albuminuria in young adults with youth-onset type 1 and type 2 diabetes. J
Diabetes Complications. 2018 Dec;32(12):1160-1168. doi:
10.1016/j.jdiacomp.2018.09.018. Epub 2018 Oct 4. PubMed PMID: 30316542; PubMed
Central PMCID: PMC6289668.


4: Vaisar T, Durbin-Johnson B, Whitlock K, Babenko I, Mehrotra R, Rocke DM,
Afkarian M. Urine Complement Proteins and the Risk of Kidney Disease Progression
and Mortality in Type 2 Diabetes. Diabetes Care. 2018 Nov;41(11):2361-2369. doi:
10.2337/dc18-0699. Epub 2018 Aug 27. Erratum in: Diabetes Care. 2019 Apr 1;:.
PubMed PMID: 30150236; PubMed Central PMCID: PMC6196831.


5: Hallan S, Afkarian M, Zelnick LR, Kestenbaum B, Sharma S, Saito R, Darshi M,
Barding G, Raftery D, Ju W, Kretzler M, Sharma K, de Boer IH. Metabolomics and
Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in
Non-diabetic CKD Patients. EBioMedicine. 2017 Dec;26:68-77. doi:
10.1016/j.ebiom.2017.10.027. Epub 2017 Oct 31. PubMed PMID: 29128444; PubMed
Central PMCID: PMC5832558.


6: Cardenas-Gonzalez M, Srivastava A, Pavkovic M, Bijol V, Rennke HG, Stillman
IE, Zhang X, Parikh S, Rovin BH, Afkarian M, de Boer IH, Himmelfarb J, Waikar SS,
Vaidya VS. Identification, Confirmation, and Replication of Novel Urinary
MicroRNA Biomarkers in Lupus Nephritis and Diabetic Nephropathy. Clin Chem. 2017
Sep;63(9):1515-1526. doi: 10.1373/clinchem.2017.274175. Epub 2017 Jun 30. PubMed
PMID: 28667184; PubMed Central PMCID: PMC5610914.


7: Nandi-Munshi D, Afkarian M, Whitlock KB, Crandell JL, Bell RA, D'Agostino R,
Saydah S, Mottl AK, Dabelea D, Black MH, Mayer-Davis EJ, Pihoker C. Vitamin D and
Albuminuria in Youth with and without Type 1 Diabetes. Horm Res Paediatr.
2017;87(6):385-395. doi: 10.1159/000475711. Epub 2017 May 29. PubMed PMID:
28554178; PubMed Central PMCID: PMC5568007.


8: Wysocki J, Goodling A, Burgaya M, Whitlock K, Ruzinski J, Batlle D, Afkarian
M. Urine RAS components in mice and people with type 1 diabetes and chronic
kidney disease. Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F487-F494. doi:
10.1152/ajprenal.00074.2017. Epub 2017 May 3. PubMed PMID: 28468961; PubMed
Central PMCID: PMC5582909.


9: Bansal N, Katz R, Robinson-Cohen C, Odden MC, Dalrymple L, Shlipak MG, Sarnak
MJ, Siscovick DS, Zelnick L, Psaty BM, Kestenbaum B, Correa A, Afkarian M, Young
B, de Boer IH. Absolute Rates of Heart Failure, Coronary Heart Disease, and
Stroke in Chronic Kidney Disease: An Analysis of 3 Community-Based Cohort
Studies. JAMA Cardiol. 2017 Mar 1;2(3):314-318. doi:
10.1001/jamacardio.2016.4652. PubMed PMID: 28002548; PubMed Central PMCID:
PMC5832350.


10: Pichler R, Afkarian M, Dieter BP, Tuttle KR. Immunity and inflammation in
diabetic kidney disease: translating mechanisms to biomarkers and treatment
targets. Am J Physiol Renal Physiol. 2017 Apr 1;312(4):F716-F731. doi:
10.1152/ajprenal.00314.2016. Epub 2016 Aug 24. Review. PubMed PMID: 27558558;
PubMed Central PMCID: PMC6109808.


11: Afkarian M, Zelnick LR, Hall YN, Heagerty PJ, Tuttle K, Weiss NS, de Boer IH.
Clinical Manifestations of Kidney Disease Among US Adults With Diabetes,
1988-2014. JAMA. 2016 Aug 9;316(6):602-10. doi: 10.1001/jama.2016.10924. PubMed
PMID: 27532915; PubMed Central PMCID: PMC5444809.


12: Dieter BP, McPherson SM, Afkarian M, de Boer IH, Mehrotra R, Short R,
Barbosa-Leiker C, Alicic RZ, Meek RL, Tuttle KR. Serum amyloid a and risk of
death and end-stage renal disease in diabetic kidney disease. J Diabetes
Complications. 2016 Nov - Dec;30(8):1467-1472. doi:
10.1016/j.jdiacomp.2016.07.018. Epub 2016 Jul 27. PubMed PMID: 27522272; PubMed
Central PMCID: PMC5435122.


13: Vrana M, Goodling A, Afkarian M, Prasad B. An Optimized Method for Protein
Extraction from OCT-Embedded Human Kidney Tissue for Protein Quantification by
LC-MS/MS Proteomics. Drug Metab Dispos. 2016 Oct;44(10):1692-6. doi:
10.1124/dmd.116.071522. Epub 2016 Aug 1. PubMed PMID: 27481856; PubMed Central
PMCID: PMC5034699.


14: Afkarian M, Katz R, Bansal N, Correa A, Kestenbaum B, Himmelfarb J, de Boer
IH, Young B. Diabetes, Kidney Disease, and Cardiovascular Outcomes in the Jackson
Heart Study. Clin J Am Soc Nephrol. 2016 Aug 8;11(8):1384-91. doi:
10.2215/CJN.13111215. Epub 2016 Jun 23. PubMed PMID: 27340284; PubMed Central
PMCID: PMC4974894.


15: Bansal N, Katz R, Himmelfarb J, Afkarian M, Kestenbaum B, de Boer IH, Young
B. Markers of kidney disease and risk of subclinical and clinical heart failure
in African Americans: the Jackson Heart Study. Nephrol Dial Transplant. 2016
Dec;31(12):2057-2064. Epub 2016 Jun 2. PubMed PMID: 27257276; PubMed Central
PMCID: PMC5146707.


16: de Boer IH, Zelnick L, Afkarian M, Ayers E, Curtin L, Himmelfarb J, Ikizler
TA, Kahn SE, Kestenbaum B, Utzschneider K. Impaired Glucose and Insulin
Homeostasis in Moderate-Severe CKD. J Am Soc Nephrol. 2016 Sep;27(9):2861-71.
doi: 10.1681/ASN.2015070756. Epub 2016 Jan 28. PubMed PMID: 26823551; PubMed
Central PMCID: PMC5004653.


17: de Boer IH, Afkarian M, Tuttle KR. The Surging Tide of Diabetes: Implications
for Nephrology. Am J Kidney Dis. 2016 Mar;67(3):364-6. doi:
10.1053/j.ajkd.2015.12.002. Epub 2015 Dec 23. PubMed PMID: 26725312; PubMed
Central PMCID: PMC5013824.


18: Afkarian M, Zelnick LR, Ruzinski J, Kestenbaum B, Himmelfarb J, de Boer IH,
Mehrotra R. Urine matrix metalloproteinase-7 and risk of kidney disease
progression and mortality in type 2 diabetes. J Diabetes Complications. 2015
Nov-Dec;29(8):1024-31. doi: 10.1016/j.jdiacomp.2015.08.024. Epub 2015 Sep 2.
PubMed PMID: 26412030; PubMed Central PMCID: PMC5389898.


19: Shao B, de Boer I, Tang C, Mayer PS, Zelnick L, Afkarian M, Heinecke JW,
Himmelfarb J. A Cluster of Proteins Implicated in Kidney Disease Is Increased in
High-Density Lipoprotein Isolated from Hemodialysis Subjects. J Proteome Res.
2015 Jul 2;14(7):2792-806. doi: 10.1021/acs.jproteome.5b00060. Epub 2015 Jun 15.
PubMed PMID: 26011469; PubMed Central PMCID: PMC4636116.


20: de Boer IH, Afkarian M, Rue TC, Cleary PA, Lachin JM, Molitch ME, Steffes MW,
Sun W, Zinman B; Diabetes Control and Complications Trial/Epidemiology of
Diabetes Interventions and Complications (DCCT/EDIC) Research Group. Renal
outcomes in patients with type 1 diabetes and macroalbuminuria. J Am Soc Nephrol.
2014 Oct;25(10):2342-50. doi: 10.1681/ASN.2013091004. Epub 2014 Jun 12. PubMed
PMID: 24925722; PubMed Central PMCID: PMC4178441.


21: Afkarian M, Hirsch IB, Tuttle KR, Greenbaum C, Himmelfarb J, de Boer IH.
Urinary excretion of RAS, BMP, and WNT pathway components in diabetic kidney
disease. Physiol Rep. 2014 May 2;2(5):e12010. doi: 10.14814/phy2.12010. Print
2014. PubMed PMID: 24793984; PubMed Central PMCID: PMC4098738.


22: Afkarian M. Diabetic kidney disease in children and adolescents. Pediatr
Nephrol. 2015 Jan;30(1):65-74; quiz 70-1. doi: 10.1007/s00467-014-2796-5. Epub
2014 Mar 19. Review. PubMed PMID: 24643739; PubMed Central PMCID: PMC4169353.


23: Mottl AK, Lauer A, Dabelea D, Maahs DM, D'Agostino RB Jr, Dolan LM, Gilliam
LK, Lawrence JM, Rodriguez B, Marcovina SM, Imperatore G, Kanakatti Shankar R,
Afkarian M, Reynolds K, Liese AD, Mauer M, Mayer-Davis EJ; SEARCH for Diabetes in
Youth Study Group. Albuminuria according to status of autoimmunity and insulin
sensitivity among youth with type 1 and type 2 diabetes. Diabetes Care. 2013
Nov;36(11):3633-8. doi: 10.2337/dc13-0568. Epub 2013 Jul 11. PubMed PMID:
23846811; PubMed Central PMCID: PMC3816857.


24: Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, de
Boer IH. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc
Nephrol. 2013 Feb;24(2):302-8. doi: 10.1681/ASN.2012070718. Epub 2013 Jan 29.
PubMed PMID: 23362314; PubMed Central PMCID: PMC3559486.


25: Afkarian M, Bhasin M, Dillon ST, Guerrero MC, Nelson RG, Knowler WC, Thadhani
R, Libermann TA. Optimizing a proteomics platform for urine biomarker discovery.
Mol Cell Proteomics. 2010 Oct;9(10):2195-204. doi: 10.1074/mcp.M110.000992. Epub
2010 May 28. PubMed PMID: 20511394; PubMed Central PMCID: PMC2957724.


26: Friedman DJ, Afkarian M, Tamez H, Bhan I, Isakova T, Wolf M, Ankers E, Ye J,
Tonelli M, Zoccali C, Kuro-o M, Moe O, Karumanchi SA, Thadhani R. Klotho variants
and chronic hemodialysis mortality. J Bone Miner Res. 2009 Nov;24(11):1847-55.
doi: 10.1359/jbmr.090516. PubMed PMID: 19419323; PubMed Central PMCID:
PMC2765930.


27: Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, Murphy TL, Murphy
KM. T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T
cells. Nat Immunol. 2002 Jun;3(6):549-57. Epub 2002 May 13. PubMed PMID:
12006974.


28: Asnagli H, Afkarian M, Murphy KM. Cutting edge: Identification of an
alternative GATA-3 promoter directing tissue-specific gene expression in mouse
and human. J Immunol. 2002 May 1;168(9):4268-71. PubMed PMID: 11970965.


29: Nguyen A, Burack WR, Stock JL, Kortum R, Chaika OV, Afkarian M, Muller WJ,
Murphy KM, Morrison DK, Lewis RE, McNeish J, Shaw AS. Kinase suppressor of Ras
(KSR) is a scaffold which facilitates mitogen-activated protein kinase activation
in vivo. Mol Cell Biol. 2002 May;22(9):3035-45. PubMed PMID: 11940661; PubMed
Central PMCID: PMC133772.


30: Murphy KM, Ouyang W, Farrar JD, Yang J, Ranganath S, Asnagli H, Afkarian M,
Murphy TL. Signaling and transcription in T helper development. Annu Rev Immunol.
2000;18:451-94. Review. PubMed PMID: 10837066.


31: Malarkannan S, Afkarian M, Shastri N. A rare cryptic translation product is
presented by Kb major histocompatibility complex class I molecule to alloreactive
T cells. J Exp Med. 1995 Dec 1;182(6):1739-50. PubMed PMID: 7500018; PubMed
Central PMCID: PMC2192241.

 

 

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