Anthony Hollenberg, MD
John Wade Professor, Medicine
The focus of my research program is the thyroid with a focus on the role of gland development and the actions of its hormones. To accomplish these goals we have built a unique program in thyroid gland development from endoderm in order to derive new therapies for hypothyroidism. Additionally, we explore thyroid hormone action and nuclear receptor signaling as a model system. Our work has uncovered a unique role for nuclear receptor co-regulatory proteins termed nuclear corepressors in thyroid hormone signaling and determining hormone sensitivity. Furthermore, we have used our understanding of thyroid hormone signaling to identify new biomarkers of its action.
My laboratory has a long-standing interest in how thyroid hormone mediates its effects in context of genomic regulation. Specifically we were amongst the first to begin to differentiate how thyroid hormone is able to stimulate both positive and negative gene regulation. Studies in this area allowed us to be able to characterize the interaction of the thyroid hormone receptor with its cofactors which are necessary for genomic regulation.
We were pioneers in the use of knock-out mouse models to validate the role of thyroid hormone receptor co-factors, specifically nuclear corepressors, in thyroid hormone signaling. These studies allowed us to demonstrate that the tissue-specific expression of co-factors determines a set hormone sensitivity. This has important ramifications for thyroid/steroid action in general. Furthermore these studies have allowed us to better understand the specificity of coregulator interactions with the thyroid hormone receptor and their role in disease.
In addition to our work on thyroid hormone action we have also had a long standing interest in the intersection of the regulation of biomarkers of thyroid hormone action including the regulation of the hypothalamic pituitary thyroid axis by thyroid hormone and other metabolic pathways. Our work has demonstrated that these pathways and others are linked at the molecular and physiological level. Furthermore, they must be considered when trying to understand the effects of thyroid hormone signaling.
Most recently, because of our interest in defining the etiology of the set point of the HPT axis, we became interested in creating a durable thyroid follicular cell model. To accomplish this we began a complete collaboration with the Kotton laboratory at Boston University and have successfully developed the molecular paradigm to develop thyroid follicular cells from ESCs or IPSCs across multiple species. Additionally we have established that these derived cells function in vivo.
- Chair, Medicine, Boston University Chobanian & Avedisian School of Medicine
- Physician-in-Chief, Boston Medical Center
- Published on 12/6/2022
Kaserman JE, Werder RB, Wang F, Matte T, Higgins MI, Dodge M, Lindstrom-Vautrin J, Bawa P, Hinds A, Bullitt E, Caballero IS, Shi X, Gerszten RE, Brunetti-Pierri N, Liesa M, Villacorta-Martin C, Hollenberg AN, Kotton DN, Wilson AA. Human iPSC-hepatocyte modeling of alpha-1 antitrypsin heterozygosity reveals metabolic dysregulation and cellular heterogeneity. Cell Rep. 2022 Dec 06; 41(10):111775. PMID: 36476855.Read at: PubMed
- Published on 12/1/2022
Shimizu H, Horibata Y, Amano I, Ritter MJ, Domae M, Ando H, Sugimoto H, Cohen RN, Hollenberg AN. Nuclear corepressor SMRT acts as a strong regulator of both ß-oxidation and suppressor of fibrosis in the differentiation process of mouse skeletal muscle cells. PLoS One. 2022; 17(12):e0277830. PMID: 36454860.Read at: PubMed
- Published on 1/24/2022
Bredella MA, McGroarty KM, Kolessin L, Bard LF, Hollenberg AN, Rutkove SB. Impact of the KL2/Catalyst Medical Research Investigator Training (CMeRIT) Program on the careers of early-stage clinical and translational investigators. J Clin Transl Sci. 2022; 6(1):e16. PMID: 35291214.Read at: PubMed
- Published on 11/16/2021
Mendoza A, Tang C, Choi J, Acuña M, Logan M, Martin AG, Al-Sowaimel L, Desai BN, Tenen DE, Jacobs C, Lyubetskaya A, Fu Y, Liu H, Tsai L, Cohen DE, Forrest D, Wilson AA, Hollenberg AN. Thyroid hormone signaling promotes hepatic lipogenesis through the transcription factor ChREBP. Sci Signal. 2021 11 16; 14(709):eabh3839. PMID: 34784250.Read at: PubMed
- Published on 9/1/2021
Vella KR, Hollenberg AN. Early Life Stress Affects the HPT Axis Response in a Sexually Dimorphic Manner. Endocrinology. 2021 09 01; 162(9). PMID: 34214171.Read at: PubMed
- Published on 8/12/2021
Ritter MJ, Amano I, Imai N, Soares De Oliveira L, Vella KR, Hollenberg AN. Nuclear Receptor CoRepressors, NCOR1 and SMRT, are required for maintaining systemic metabolic homeostasis. Mol Metab. 2021 11; 53:101315. PMID: 34390859.Read at: PubMed
- Published on 4/20/2021
Posabella A, Alber AB, Undeutsch HJ, Droeser RA, Hollenberg AN, Ikonomou L, Kotton DN. Derivation of Thyroid Follicular Cells From Pluripotent Stem Cells: Insights From Development and Implications for Regenerative Medicine. Front Endocrinol (Lausanne). 2021; 12:666565. PMID: 33959101.Read at: PubMed
- Published on 4/20/2021
Finn PW, Abel D, Amin A, Anderson ME, Carethers JM, Coleman DL, Curtis AB, Geraci MW, Gladwin MT, Hollenberg A, Parmacek MS, Robbins RJ. Voices for Social Justice and Against Racism: An AAIM Perspective. Am J Med. 2021 07; 134(7):930-934. PMID: 33848502.Read at: PubMed
- Published on 11/24/2020
Major-Pedersen A, McCullen MK, Sabol ME, Adetunji O, Massaro J, Neugut AI, Sosa JA, Hollenberg AN. A joint industry-sponsored data monitoring committee model for observational, retrospective drug safety studies in the real-world setting. Pharmacoepidemiol Drug Saf. 2021 01; 30(1):9-16. PMID: 33179845.Read at: PubMed
- Published on 10/1/2020
Kahn JH, Goddi A, Sharma A, Heiman J, Carmona A, Li Y, Hoffman A, Schoenfelt K, Ye H, Bobe AM, Becker L, Hollenberg AN, Cohen RN. SMRT Regulates Metabolic Homeostasis and Adipose Tissue Macrophage Phenotypes in Tandem. Endocrinology. 2020 10 01; 161(10). PMID: 32770234.Read at: PubMed
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