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Amanda M. Ackermann, MD, PhD
Attending Physician
Dr. Ackermann studies diabetes (types 1 and 2) and congenital hyperinsulinism using mouse models, cell lines, and primary human tissue. She aims to identify novel pathways regulating beta cell insulin secretion, leading to innovative therapeutic strategies for these disorders. Current studies include in vivo mouse physiology, ex vivo human islet physiology, CRISPR-Cas9 gene editing, epigenetic modification, and single-cell functional genomics.
Bio
Dr. Ackermann’s basic and translational research into type 1 diabetes, type 2 diabetes, and congenital hyperinsulinism involves several lines of investigation.
She studies beta cell function genomics in diabetes by performing single-cell functional imaging followed by single-cell RNA-sequencing on islet cells from human donors with or without type 1 or type 2 diabetes. Dr. Ackermann also studies epigenetic regulation of beta cell differentiation and function. Based on patients with a rare genetic disorder who exhibit beta cell dysfunction, she and her team generated mouse models in which epigenetic regulators are specifically deleted in beta cells or beta cell progenitors. She is currently characterizing these mice and thus far has identified a difference in beta cell glucose-stimulated insulin secretion.
In addition, Dr. Ackermann performs high-throughput sequencing analyses of islet cells to determine the molecular mechanisms of congenital hyperinsulinism and cell-autonomous effects of beta cell insulin hypersecretion. These investigations complement functional studies performed by collaborators, and together identify new mechanisms regulating beta cell insulin secretion.
Current clinical research by Dr. Ackermann involves vitamin E supplementation in hyperinsulinism/hyperammonemia (HI/HA) syndrome. Pre-clinical data in human cell lines and mice suggest that vitamin E (alpha-tocopherol) inhibits activity of the glutamate dehydrogenase (GDH) enzyme. As there are no current treatments to target the GDH enzyme, this pilot study by Dr. Ackermann and her team will assess short-term tolerability and efficacy of vitamin E.
A second current clinical project by Dr. Ackermann involves reducing time to treatment of diabetic ketoacidosis in the Emergency Department. This multidisciplinary quality improvement project aims to reduce treatment variability and optimize treatment timing for patients with type 1 diabetes who present to the ED with diabetic ketoacidosis, in order to reduce complications and morbidities, improve patient satisfaction, and enhance efficiency and value of care.
Education and Training
BS, Southwestern University (Biology and Chemistry), 2002
PhD, Vanderbilt University (Molecular Physiology and Biophysics), 2008
MD, Vanderbilt University, 2010
Fellowship, Children's Hospital of Philadelphia (Pediatric Endocrinology), 2016
MS, University of Pennsylvania (Translational Research, Entrepreneurial Science), 2019
Titles and Academic Titles
Attending Physician
Associate Program Director, Pediatric Endocrinology Fellowship Program
Assistant Professor of Pediatrics
Professional Memberships
American Academy of Pediatrics, 2010-
Pediatric Endocrine Society, 2012-
Philadelphia Endocrine Society, 2012-
Society for Pediatric Research, 2012-
Endocrine Society, 2014-
Professional Awards
Postdoctoral Fellowship Award, Juvenile Diabetes Research Foundation, 2014
Young Investigator Trainee Award, Eastern Society for Pediatric Research, 2015
Outstanding Poster Award, Joint Meeting of the Islet Study Group & Beta Cell Workshop, 2015
Clinical Scholar Award, Pediatric Endocrine Society, 2018
Publication Highlights
Pubmed:
Ackermann AM, Moss, NG, Kaestner, KH. GABA and artesunate do not induce pancreatic alpha-to-beta cell trans-differentiation in vivo. Cell Metab. 2018 Nov; 28(5):787-792.e3. PMID: 30057067
Li C, Ackermann AM, Patel P, Chen P, Boodhansingh KE, Givler S, Bhatti TR, Liu C, Schug J, Doliba N, Matschinsky FM, Nissim I, Kaestner KH, Naji A, Adzick NS, Stanley CA, De León DD. Functional and metabolic evaluation of islets from infants with hyperinsulinism due to loss of function mutations of ATP-dependent potassium channels. Diabetes. 2017 Jul; 66(7):1901-1913. PMCID: PMC5482088
Ackermann AM, Zhang J, Heller A, Briker A, Kaestner KH. High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting. Mol Metab. 2017 Jan; 6(3):236-244. PMCID: PMC5323890
Ackermann AM, Wang P, Schug J, Naji A, Kaestner KH. Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes. Mol Metab. 2016 Jan; 5(3):233-244. PMCID: PMC4770267
Ackermann AM, Palladino AA. Managing congenital hyperinsulinism: improving outcomes with a multidisciplinary approach. Research and Reports in Endocrine Disorders. 2015 Jul; 5: 103-117, 2015
Links of Interest
Ackermann Lab Website (UPenn)
Clinical Website (CHOP)