BIOGRAPHICAL SKETCH
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NAME: Salehi, Marzieh
POSITION TITLE: Associate Professor
eRA COMMONS USER NAME (credential, e.g., agency login): SALEHIMZ
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
Completion
Date
MM/YYYY
Tehran University of Medical Sciences, Tehran, Iran
MD
1986-1992
Northwestern University, Feinberg School of
Medicine, Chicago, IL
MS
2003-2004
University of Cincinnati, College of Medicine,
Cincinnati, OH
MS
2007-2010
FIELD OF STUDY
Medicine
Clinical Investigation
(completed 4/10 of
required credits)
Clinical and Translational
Research
A. Personal Statement
I am a board certified endocrinologist and translational investigator with more than 10 years of experience in
human research related to metabolism, obesity, and diabetes. I started my academic career as a clinician and
by cultivating an active subspecialized practice I became recognized as a regional and national expert in
PCOS with metabolic syndrome, diabetes related to islet autotransplantation as well as glucose abnormalities
after bariatric surgery. The latter condition has led to majority of my research effort, for which I have been
continuously funded for 10 years (NIH, AHA, and ASBMS), with my recent R01 application funded in 2015
(NIDDK). In early stage of my career I had become proficient in performing complex clinical research protocols
in glucose metabolism and incretin physiology, and soon sought to teach these methodologies to junior
investigators and trainees. These are state-of-the-art experimental procedures that have been in use since
mid-nineteen seventies to assess metabolic function. As my clinical expertise in glucose abnormalities after
bariatric surgeries advanced and my network of collaboration with clinician scientists as well as bariatric
surgeons expanded, my laboratory research became more focused on the investigation of the role of neural
factor and gastrointestinal (GI) hormones, particularly glucagon like peptide-1 (GLP-1), in glucose homeostasis
after weight-loss surgeries in individuals with and without the late-complication of hypoglycemia syndrome.
B. Positions and Honors
Positions and Employment
1998-2001 Internship & Residency: Internal Medicine, Lincoln Medical and Mental Health Center, Weill College
of Medicine of Cornell University, Bronx, NY
2001-2003 Fellowship: Endocrinology, Beth Israel Medical Center, Albert Einstein College of Medicine, NY, NY
2003-2004 Instructor of Medicine, Northwestern University Feinberg School of Medicine, Department of
Medicine, Division of Endocrinology, Chicago, IL
2004-2005 Research Instructor of Medicine, University of Cincinnati, Department of Medicine, Division of
Endocrinology, Cincinnati, OH
2006-2012 Assistant Professor of Medicine, University of Cincinnati, Department of Medicine, Division of
Endocrinology, Cincinnati, OH
2012- 12/31/ 2015 Associate Professor of Medicine, University of Cincinnati, Department of Medicine, Division
of Endocrinology, Cincinnati, OH
2016-2017 Director, Clinical and Translational Research Center (CTRC), Cedars Sinai Medical Center, Los
Angeles, CA
Jan 2016 - Associate Professor, Department of Biomedical Science, Department of Medicine, Director of
Clinical Research, Diabetes & Obesity Research Institute, Cedars Sinai Medical Center, Los Angeles, CA
Other Experience and Professional Memberships
1998-2011 Member, American College of Physicians
2011Fellow, American College of Physicians
2001Member, American Association of Clinical Endocrinologists
2001Member, Endocrine Society
2001Member, American Diabetes Association
2006Member, American Society of Bariatric Surgery
2014Member, Obesity Society
Honors
2003
2003
2006
2007
Pfizer Outstanding Achievement in the Advancement of Endocrinology Science Award
Endocrine Society travel grant recipient
Ursich Research Award, VAMC/University of Cincinnati
Dean’s Scholar Award, University of Cincinnati
C. Contributions to Science
1. The role of GLP-1 in islet function and gastric emptying in human
Postprandial glucose metabolism in humans are tightly regulated as a result of enterinsular axis activity.
Glucagon like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are two main gut
hormones that collectively contribute to more than half of insulin response to meal ingestion in human. Using a
novel methodology – validated by our group - we were able to show that endogenous GLP-1 stimulates
postprandial insulin response while decreases glucagon secretion in healthy individuals. Using the same
setting, blocking GLP-1r during hyperglycemic clamp combined with meal ingestion, we were also able to show
that GLP-1 contribution to insulin secretion after meal ingestion was not affected in patients with well controlled
diabetes. Moreover, we were able to show that endogenous GLP-1 has a trivial effect on gastric emptying.
These findings advanced our knowledge in glucose and incretin physiology in normal and disease.
a.
Salehi M, Vahl T, D’Alessio D (2008). Regulation of islet hormone release and gastric emptying by
endogenous GLP-1 following glucose ingestion. J Clin Endocrinol Metab. 93 (12): 4909-4916. PMID:
18827000 PMCID: PMC2626449
b.
D’Alessio D, Aulinger B, Salehi M (2008). The incretin effect: Regulation of insulin secretion and
glucose tolerance by GI hormones. In: Greenbaum and Harrison eds. Diabetes: Translating research into
practice. Informa Healthcare, 5th edition.
c.
Salehi M, Aulinger B, Prigeon RL, D’Alessio DA (2010). Effects of endogenous GLP-1 on insulin
secretion in type 2 diabetes. Diabetes. 59(6):1330-7. PMID: 20215429 PMCID: PMC2874693
d.
Salehi M, Aulinger B, D’Alessio D (2008). Targeting β-cell mass in Type 2 diabetes: Promise and
limitations of new drugs based on incretins. Endocr Rev.29(3):367-79. PMID: 18292465 PMCID:
PMC2528856
e.
Salehi M, Aulinger B, D’Alessio DA (2012). Effect of glycemia on plasma incretins and the incretin
effect during oral glucose tolerance test. Diabetes. 61(11):2728-33. PMID: 22733799 PMCID: PMC3478560
f.
Salehi M (2016). The role of Incretins in Insulin Secretion. In: Leonid Poretsky eds. Principles of
Diabetes Mellitus. Springer. U.S. 3rd edition – doi:10.1007/978-3-319-20797-1
2. Altered glucose metabolism after gastric bypass surgery
The substantial impact of gastric bypass on glucose metabolism is exemplified by the syndrome of
hyperinsulinemia hypoglycemia, which occurs in a small subset of subjects, but has not been reported after
restrictive bariatric procedures or sleeve gastrectomy. The etiology for this late-complication of gastric bypass
is not known and therapeutic options are very limited. Given my national recognition as the clinical expert in
this filed we were able to enroll a large number of affected individuals in meal studies. We reported for the first
time that hyperinsulinemic hypoglycemia after RYGB is associated with low insulin clearance, lack of glucagon
response to hypoglycemia in addition to enhanced insulin and GLP-1 secretion compared to those without
hypoglycemia after this procedure. Our observations have changed our knowledge and understanding about
this condition significantly and generated hypothesis to be tested for treatment of this condition.
a.
Chuang J, Baum L, D’Alessio DA, Salehi M (2012). Glycemic profile assessment using continuous
glucose monitoring in patients with and without hypoglycemia after gastric bypass surgery. American
Diabetes Association, 72nd Scientific Session, Philadelphia, PA.
b.
Salehi M, D’Alessio DA (2013). Going with the flow: Adaptation of β-Cell function to glucose fluxes
after bariatric surgery. Diabetes. 62(11):3671-3. PMID:24158997 PMCID: PMC3806591
c.
Salehi M, Gastaldelli A, D’Alessio DA (2014). Altered islet function and insulin clearance cause
hyperinsulinemia in gastric bypass patients with symptoms of postprandial hypoglycemia. J Clin Endocr
Metabol,99(6):2008-17. PMID:24617664 PMC4037736
3. Altered GLP-1 activity after gastric bypass surgery (enteroinsular axis - hormonal factors)
Diabetes remission after gastric bypass surgery has been well recognized. Glycemic effects of this surgery is
immediate and way before any significant weight loss. The weight-independent effects of gastric bypass
surgery to improve diabetes have been mostly attributed to altered postprandial islet function as a result of
changes in gut hormone secretion or actions. Our studies using novel methodology including infusion of GLP-1
antagonists showed for the first time that gastric bypass surgery enhances GLP-1-stimulated insulin response
to meal ingestion. Also we have demonstrated that in individuals with post gastric bypass hypoglycemia,
blocking GLP-1 receptor corrects hypoglycemia. Beyond novel scientific advancement, in collaboration with
renowned physiologists we were able to advance our methodology to include mathematical modeling to
measure glucose flux as well as beta-cell function.
a.
Salehi M, Prigeon RL, D’Alessio DA (2011). Gastric bypass surgery enhances glucagon-like peptide 1
stimulated postprandial insulin secretion in human. Diabetes. 60(9): 2308-14. PMID: 21868791 PMCID:
PMC3161307
b.
Salehi M, Gastaldelli A, D’Alessio DA (2014). Blockade of glucagon-like peptide 1 receptor corrects
postprandial hypoglycemia after gastric bypass. Gastroenterology, 146: 669-680. PMID: 24315990
PMC3943944
c.
Salehi M, Gastaldelli A, D’Alessio DA (2014). Evidence from a single individual that increased plasma
GLP-1 and GLP-1-stimulated insulin secretion after gastric bypass are independent of foregut exclusion.
Diabetologia, 57 (7): 1495-99. PMID: 24797288 PMC4077274
d.
Salehi M and D’Alessio DA (2014). Effects of glucagon like peptide-1 to mediate glycemic effects of
weight loss surgery. Rev Endocr Metab Disord.15(3):171-9. doi: 10.1007/s11154-014-9291-y. PMC4119589
e.
Salehi M and D’Alessio DA (2016). Mechanisms of Surgical Control of Type 2 Diabetes: GLP-1 is the
Key Factor – Maybe. Surg Obes Rel Dis. 12(6):1230-5 PMID: 27568473 PMC5002889
4. Altered enteroinsular axis activity (non-hormonal factors) after gastric bypass surgery:
In non-operated individuals postprandial insulin secretion is regulated by glucose-dependent GI hormones as
well as non-hormonal factors. While the contribution of gut hormones on islet function have not been fully
understood, the effects of non-hormonal components of the enteroinsular axis (i.e., nutrient and neural
stimulation) after GB are completely unknown. Using novel methodologies of sham feeding as well as and
hypoglycemic clamp and meal ingestion we were able to show that insulin response to meal ingestion after
gastric bypass surgery is not glucose dependent suggestive of non-hormonal factors involvement. The
sophisticated methodology used in these studies have laid groundwork for future mechanistic studies in
glucose physiology and neural signaling in human.
a.
Salehi M, Prigeon RL, Gastaldelli A, D’Alessio DA (2011). Differential effect of sham feeding on meal
glucose tolerance in hypoglycemic vs. asymptomatic individuals after gastric bypass surgery. American
Diabetes Association, 71st Scientific Session, San Diego, CA.
b.
Barrera JG, Baum L, Woods S, D’Alessio DA, Salehi M (2012). The effects of sham feeding and GLP-1
receptor blockade on subsequent food intake in patients with gastric bypass surgery. The Endocrine
Society’s 94th, Houston, TX.
c.
Salehi M, Woods SC, D’Alessio DA (2015). Gastric bypass alters both glucose-dependent and glucoseindependent regulation of islet hormone secretion. Obesity, 23(10):2046-52 PMID: 26316298 PMC: 4586360
5. The effect of islet autotransplantation and total pancreatectomy on glucose metabolism
Patients with chronic pancreatitis often suffer from incapacitating pain that may be relieved by surgical
resection of the pancreas. Islet autotransplantation (IAT) can potentially alleviate the severe and clinically
problematic diabetes that inevitably occurs after total pancreatectomy. While isolated cases of long-term
success had been reported natural history of islet function following IAT was largely unknown. My work as the
endocrinologist has improved diabetes management in this specific cohort with GI derangement as well as
advanced our knowledge about long term effect of IAT on islet function.
a.
Salehi M, Rilo HLR, Ahmad SA, Matthews JB, Lowy AM, D’Alessio DA (2006). Stability of Insulin
Secretion Following Islet Autotransplantation. American Diabetes Association, Washington DC
b.
Wilson GC, Sutton JM, Salehi M, et al (2013). Surgical outcomes after total pancreatectomy and islet
cell autotransplantation in pediatric patients. Surgery;154(4):777-83 PMID: 24074415.
c.
Wilson GC, Sutton JM, Smith MT, Schmulewitz N, Salehi M, Choe KA, Brunner JE, Abbott DE,
Sussman JJ, Ahmad SA (2015). Total pancreatectomy with iselt cell autotransplantation as the initial
treatment for minimal-change chronic pancreatitis.HPB (Oxford), 17(3):232-8. PMID:25297689
d.
Wilson GC, Sutton JM, Smith MT, Schmulewitz N, Salehi M, Choe KA, Levinsky NC Jr, Brunner JE,
Abbott DE, Sussman JJ, Edwards MJ, Ahmad SA (2015). Completion pancreatectomy and islet cell
autotransplantation as salvage therapy for patients failing previous operative interventions for chronic
pancreatitis. Surgery. PMID: 26173686
1. Research Support
Ongoing Research Support:
R01DK105379 – $1,900,000 direct cost 06/2015- 06/2020 Salehi (PI)
The weight-independent effects of bariatric surgeries on islet cell function
The aim of this project is to study the underlying mechanisms by which gastric bypass and sleeve
gastrectomy alter postprandial glucose metabolism independent of weight loss focusing on enteroinsularaxis function
Completed Research Support:
--NCAT/UL1TR - $1,176,021 direct cost 07/01/16-05/31/21 Dubinet (PI)
UCLA Clinical and Translational Science Institute (CTSI) – The purpose of this is to support and encourage
clinical at Cedars-Sinai Medical Center, UCLA, Harbor-UCLA Medical Center, Drew University, and within
the communities these institutions serve
Role: co-leader PCI (Jan 2016- Jan 2017)
--K23 DK083554 -07/01/2009 – 06/30/2015 Salehi (PI)
Hormonal and neural control of insulin secretion following gastric bypass surgery
The aims of this project were to gain expertise in the performance, assessment and interpretation of
measures of insulin secretion in relationship with the function of neural and hormonal regulatory factors in
general as well as in the state of post gastric bypass surgery.
--AHA, Scientific Development Grant, National Program- 0635181N- 07/01/2006-6/30/2009
The role of GLP-1 in glucose metabolism and weight loss following gastric bypass surgery
The aims of this project were to study the effect of gastric bypass surgery on incretin effect and GLP-1
contribution to insulin secretion in patients with diabetes.
Role: PI
--American Society of Bariatric Surgery, Research Grant -07/01/2006-06/30/2007
Glucose metabolism following gastric bypass surgery
The goal was to study the overall effect of gastric bypass on glucose metabolism and islet function.
Role: PI
--R01 DK57900-04 -6/1/04-5/31/08 D’Alessio (PI)
GLP-1 in normal and abnormal glucose tolerance
The aims of this project were to determine the mechanisms by which GLP-1 regulates insulin secretion.
Role: co-investigator
--VA Merit Award -10/1/07-7/01/09 D’Alessio (PI)
Pathogenesis of the abnormal incretin effect in type 2 diabetes
This project was directed at understanding the role of GLP-1 secretion and action in type 2 diabetes.
Role: co-investigator