Raff Laboratory
Location
Aurora St. Luke's Medical Center
2801 W. KK River Pkwy., Suite 260
Milwaukee, WI 53215
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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(Rolon S, Huynh C, Guenther M, Gardezi M, Phillips J, Gehrand AL, Raff H.) Physiol Rep. 2021 Jan;9(1):e14663 PMID: 33393733 PMCID: PMC7780235 SCOPUS ID: 2-s2.0-85099269848 01/05/2021
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(Tjoe JA, Piacentine LB, Papanek PE, Raff H, Richards J, Harkins AL, Yin J, Ng AV.) Support Care Cancer. 2020 Dec;28(12):6095-6104 PMID: 32314053 SCOPUS ID: 2-s2.0-85084088106 04/22/2020
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(Kannankeril J, Carroll T, Findling JW, Javorsky B, Gunsolus IL, Phillips J, Raff H.) J Endocr Soc. 2020 Oct 01;4(10):bvaa107 PMID: 32935666 PMCID: PMC7480956 09/17/2020
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(Raff H, Phillips JM, Simpson PM, Weisman SJ, Hainsworth KR.) Pain Rep. 2020 Jul-Aug;5(4):e836 PMID: 32766470 PMCID: PMC7382552 SCOPUS ID: 2-s2.0-85099731746 08/09/2020
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(Gehrand AL, Phillips J, Malott K, Raff H.) Endocrinology. 2020 07 01;161(7) PMID: 32459830 PMCID: PMC7310600 SCOPUS ID: 2-s2.0-85087096075 05/28/2020
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(Wissner Greene L, Geer EB, Page-Wilson G, Findling JW, Raff H.) J Endocr Soc. 2020 Feb 01;4(2):bvz012 PMID: 32099949 PMCID: PMC7033035 02/27/2020
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(Rolon S, Huynh C, Guenther M, Gardezi M, Phillips J, Gehrand AL, Raff H.) Physiol Rep. 2019 12;7(24):e14318 PMID: 31876126 PMCID: PMC6930936 SCOPUS ID: 2-s2.0-85077197377 12/27/2019
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A commentary on Diagnosing Cushing's disease in the context of renal failure.
(Raff H, Cohen EP, Findling JW.) Eur J Endocrinol. 2019 Oct;181(4):C9-C11 PMID: 31349218 SCOPUS ID: 2-s2.0-85072229843 07/28/2019
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(Raff H, Phillips JM.) J Endocr Soc. 2019 Aug 01;3(8):1631-1640 PMID: 31403090 PMCID: PMC6682408 08/14/2019
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(Gehrand AL, Phillips J, Malott K, Raff H.) Endocrinology. 2019 07 01;160(7):1719-1730 PMID: 31166572 SCOPUS ID: 2-s2.0-85068887045 06/06/2019
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(Greene LW, Geer EB, Page-Wilson G, Findling JW, Raff H.) J Endocr Soc. 2019 Apr 01;3(4):763-772 PMID: 30963134 PMCID: PMC6446888 04/10/2019
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Glucocorticoid Receptor Mutations and Hypersensitivity to Endogenous and Exogenous Glucocorticoids.
(Santen RJ, Jewell CM, Yue W, Heitjan DF, Raff H, Katen KS, Cidlowski JA.) J Clin Endocrinol Metab. 2018 10 01;103(10):3630-3639 PMID: 30020469 PMCID: PMC6179182 SCOPUS ID: 2-s2.0-85054465582 07/19/2018