Raff Laboratory
Location
Health Research Center
H4200
General Interests
Physiology, Endocrinology, Clinical Chemistry
Research Areas
Hypoxia is common with preterm birth and may lead to long-term effects on the adult hypothalamic-pituitary-adrenal (HPA) axis that are sexually dimorphic due to neonatal androgens. Although the adult rat adrenal does not express appreciable CYP17 activity, the neonatal rat adrenal may synthesize androgens that could be a critical local factor in the development of adrenal function. We evaluated these phenomena by pretreating the neonatal rats on postnatal days (PD) 1, 6, 13, 20 with flutamide (a non-steroidal androgen receptor antagonist) at a standard or a high-dose (10 mg/kg or 50 mg/kg) compared to vehicle control. One day later, neonatal rats were exposed to acute hypoxia and blood was sampled. Our studies suggest that neonatal androgens play a role in regulation of adrenal function that is sexually dimorphic and changes during early development.
Premature birth is a major public health problem worldwide and can lead to transient adrenal insufficiency. The stress of premature birth includes the inability to control blood glucose and maintain normal oxygenation leading to hypoxia. Corticosteroid administration enhances surfactant production and improves oxygenation in preterm humans. However, corticosteroids can also have negative consequences. We have validated a rat model of separation and hypoxia on post-natal day (PD) 2 that emulates the stress and treatment of hypoxia in the preterm human infant. We hypothesized that the role of endogenous glucocorticoids in our neonatal rat model of preterm birth can be evaluated using the novel selective glucocorticoid receptor (GR) antagonist CORT113176 (Corcept) which is devoid of progesterone receptor effects. The differential effects of CORT113176 based on age and target tissue indicate that GR regulation changes in early development in our animal model of human prematurity. These findings may have significant implications in the treatment of hypoxia and transient adrenal insufficiency in the preterm infant as well as give insight into the nuances of the control of glucocorticoid receptor function.
Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA) is established as a reliable screening test and recommended as a first-line test for Cushing’s syndrome. However, liquid chromatography-tandem mass spectrometry (LCMS), validated to measure salivary cortisol (F) and cortisone (E), has been proposed to be superior diagnostically as well as helpful in detecting saliva contaminated with topical hydrocortisone (i.e. cortisol). So far we have measured EIA-F, LCMS-F, and LCMS-E in 913 consecutive late-night saliva samples from patients suspected of Cushing’s syndrome. EIA-F appears to be superior to LCMS-F in identifying CD patients with milder hypercortisolism using established diagnostic cutoffs. Neither LCMS-E nor F/E ratio improved the diagnostic sensitivity in newly diagnosed CD or persistent/recurrent CD after pituitary surgery. We suggest that late-night salivary cortisol measured by EIA provides the best sensitivity for CD diagnosis.
Current Members
Ashley Gehrand, MS
Research Associate
Jonathan Phillips, BS
Research Associate
Santiago Rolon
M3 Medical Student
Pathway Research Project
Kyle Welhouse
M2 Medical Student
Pathway Research Project
Molly Murray
M1 Medical Student
Pathway Student
Josh Kannakeril, MD
Clinical Endocrine Fellow
Alumni/Former Trainees
Clinical Fellows (Research)
- Thomas P. Segerson, MD – Research Fellow
- Victor O. Waters, MD – Critical Care Fellow
- Santo J. Diaz, MD – Critical Care Fellow
- Manoj H. Majmudar, MD – Critical Care Fellow
- Robert C. Brickner, MD – Endocrine Metabolic Fellow
- Pennapa Chan, MD – Endocrine-Metabolic Fellow
- Scott Brock, MD – Endocrine-Metabolic Fellow
- Sandra L. Ettema, MD, PhD, CCC-SLP – Otolaryngology Resident
- Vidya Kidambi, MD – Endocrine-Metabolic Fellow
- Ty Carroll, MD – Endocrine-Metabolic Fellow
- Jay Mepani, MD-Endocrine-Metabolic Fellow
- Michael Einstein, MD – GI Fellow
- Giovanna Caprirolo, MD – Pediatric Critical Care Fellow
- Mohamed Tahsin Jouhari, MD – Pediatric Critical Care Fellow
- Neil Reisinger, MD – Chief Medical Resident
- Nebiyu Biru, MD – Chief Medical Resident
- Satyanisth Agrawal, MD – GI Fellow
- Brian Rajca, MD – GI Fellow
- Julia Leo, MD – GI Fellow
- Veena Kumaravel, MD – GI Fellow
- Jonathan Fahler, MD – GI Fellow
Post Doctoral Research Fellow
Paula. E. Papanek, PhD
Graduate Students
Eric D. Bruder, MS – University of Wisconsin, Milwaukee
Medical Student Research Trainees – Medical College of Wisconsin
- Timothy P. Roarty
- Maryam Ivanoff
- Steven C. Griffen
- Saeid Kohandarvish
- Mark H. Rossing
- Sandra K. Doepker
- Pedro Lucero
- Anne Nagler
- Jody VanHoof
- Karl Johnson (Clinician Scientist Pathway Advisor, 2011-2014; T35 Training Grant from National Heart, Lung, Blood Institute (NHLBI))
- Jonathan Bodager (Clinical Scientist Pathway Advisor, 2013-2016)
- Nasha Nensey (Physician Scientist – Molecular and Cellular Research Pathway Advisor, 2014-2017)
- Adam Goldenberg (Physician Scientist – Molecular and Cellular Research Pathway); Advisor, 2016-2019; T35 Training Grant from the National Heart, Lung, Blood Institute (NHLBI)
- Christine Huyhn (Quality Improvement and Patient Safety Pathway); Research Advisor 2017, Dr. Michael J. Dunn Medical Student Summer Research Training Fellowship)
Undergraduate Summer Trainees
- A. Joseph Tector, III – Indiana University
- Edward Stauber (1997 Endocrine Society Student Research Fellow) – University of Wisconsin
- Genevieve Schmitt – College of the Holy Cross
- Seth Auger – University of Dayton
- Judson Werner – University of Wisconsin
- Michael Patrick Kehoe – University of Wisconsin
- Jonathan Klinger – Marquette University
- John P. Tucker – University of Wisconsin
- Jennifer Taylor – Northwestern University
- Michael Nord – University of Minnesota
- Kimberli Kamer – University of Wisconsin
- Mitchell Guenther – Lawrence University
- Christopher Wean – Renssalaer Polytechnic Institute
- Kathan Chintamaneni – Washington University of St. Louis
- Kristin Prewitt – University of Wisconsin
- Thomas Gessert – University of Wisconsin
- Mack Jablonski – Lawrence University
- Cole Leonovicz – University of Miami
- Emily Waples – Duke University
- Minhal Gardezi – Wellesley College
- Maya Guenther – Lawrence University
- Matthew Schulgit – University of Wisconsin
- Hana Siddiqui – University of Wisconsin
Recent Publications
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(Olsen CM, Glaeser BL, Szabo A, Raff H, Everson CA.) Physiol Behav. 2023 Dec 01;272:114372 PMID: 37805135 SCOPUS ID: 2-s2.0-85173957688 10/08/2023
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Salivary Cortisol Dynamics After Mild Traumatic Brain Injury.
(Musacchio S, Kallenbach MD, Huber DL, Raff H, Johnson BD, Leddy J, McCrea MA, Meier TB, Nelson LD.) J Head Trauma Rehabil. 2023 Jul-Aug 01;38(4):E318-E327 PMID: 36696236 PMCID: PMC10329977 SCOPUS ID: 2-s2.0-85164269490 01/26/2023
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Recognition of Nonneoplastic Hypercortisolism in the Evaluation of Patients With Cushing Syndrome.
(Findling JW, Raff H.) J Endocr Soc. 2023 Jul 03;7(8):bvad087 PMID: 37440963 PMCID: PMC10334485 07/13/2023
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Genetic background in the rat affects endocrine and metabolic outcomes of bisphenol F exposure.
(Wagner VA, Holl KL, Clark KC, Reho JJ, Dwinell MR, Lehmler HJ, Raff H, Grobe JL, Kwitek AE.) Toxicol Sci. 2023 Jun 28;194(1):84-100 PMID: 37191987 PMCID: PMC10306406 SCOPUS ID: 2-s2.0-85164065947 05/16/2023
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(Gehrand AL, Phillips JM, Raff H.) Am J Physiol Regul Integr Comp Physiol. 2023 Jun 01;324(6):R708-R719 PMID: 36912474 SCOPUS ID: 2-s2.0-85159739229 03/14/2023
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Alcohol-induced Cushing syndrome: report of eight cases and review of the literature.
(Surani A, Carroll TB, Javorsky BR, Raff H, Findling JW.) Front Endocrinol (Lausanne). 2023;14:1199091 PMID: 37409223 PMCID: PMC10319132 07/06/2023
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(Raff H, Glaeser BL, Szabo A, Olsen CM, Everson CA.) Stress. 2023 Jan;26(1):2185864 PMID: 36856367 PMCID: PMC10339708 SCOPUS ID: 2-s2.0-85150079770 03/02/2023
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(Ferrari LF, Rey C, Ramirez A, Dziuba A, Zickella J, Zickella M, Raff H, Taylor NE.) Sci Rep. 2022 Nov 11;12(1):19348 PMID: 36369350 PMCID: PMC9652451 SCOPUS ID: 2-s2.0-85141733424 11/13/2022
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(Raff H.) Pituitary. 2022 Oct;25(5):698-700 PMID: 35334030 SCOPUS ID: 2-s2.0-85127277574 03/26/2022
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Lipid signatures of chronic pain in female adolescents with and without obesity.
(Gonzalez PA, Simcox J, Raff H, Wade G, Von Bank H, Weisman S, Hainsworth K.) Lipids Health Dis. 2022 Aug 30;21(1):80 PMID: 36042489 PMCID: PMC9426222 SCOPUS ID: 2-s2.0-85136987097 08/31/2022
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(Medda R, Raff H, Shaker J, Guda N.) Am J Gastroenterol. 2022 May 01;117(5):813-814 PMID: 35080511 SCOPUS ID: 2-s2.0-85129996587 01/27/2022
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Interaction of chronic pain, obesity and time of day on cortisol in female human adolescents.
(Raff H, Phillips J, Simpson P, Weisman SJ, Hainsworth KR.) Stress. 2022 Jan;25(1):331-336 PMID: 36330600 SCOPUS ID: 2-s2.0-85141327101 11/05/2022