Dale J. Hamilton, MD

Elaine and Marvy A. Finger Distinguished Chair for Translational Research in Metabolic Disorders & Professor of Clinical Medicine, Academic Institute
Full Clinical Member, Research Institute
Director, Center for Bioenergetics
Houston Methodist
Weill Cornell Medical College

Center for Bioenergetics


Dr. Hamilton’s professional career tract has provided the expertise, leadership, and experience to direct the Center for Bioenergetics at Houston Methodist Research Institute. His education was in cellular molecular biology and medicine, and post-graduate training in medicine and endocrinology, as well as laboratory research. His early professional career combined clinical practice and graduate medical education. The transition to translational research began in 2002 when he formed collaborations with colleagues involving clinical treatment trials and orthotopic human islet transplantation. By 2006 his research focus had narrowed to translational issues related to mitochondrial substrate oxidation and energy transfer in failing organ systems such as the human heart.

Description of Research

In 2013, Dr. Hamilton established a bioenergetic research initiative at Houston Methodist Research Institute with the objective of identifying mechanisms of altered energy transduction in disease states, especially those involving high energy tissues. Early and ongoing investigations focus on myocardial energetics in the failing heart. Evolving projects now include the mechanistic study of energy strategies in neoplasia and bioenergetic changes associated with estrogen deficiency. A recent novel but growing project addresses the challenge of transferring functional mitochondria into energy altered tissue such as the failing cardiomyocyte or growing neoplastic cell. The investigative methods include the use of pre-clinical models, tissue cultures and human tissue for analysis. Oxygen consumption, respiratory coupling and glycolytic energy transfer using genomics, metabolomic and proteomic methods are also studied. The team includes basic science specialists in biochemistry and cell biology as well as clinical investigators in cardiology, endocrinology and cardiothoracic surgery. These results have been communicated to the local and national scientific community; positive feedback on these results has strengthened the lab’s ability to design a realistic research plan.

Areas Of Expertise

Diabetes Bioenergetics & Molecular Medicine Endocrine disorders Diabetic complications
Education & Training

Residency, Baylor College of Medicine
Clinical Fellowship, Baylor College of Medicine
MD, Saint Louis University

The Role of Calcium Signaling in Melanoma
Zhang, H, Chen, Z, Zhang, A, Gupte, AA & Hamilton, DJ 2022, , International journal of molecular sciences, vol. 23, no. 3, 1010. https://doi.org/10.3390/ijms23031010

Polymer-Functionalized Mitochondrial Transplantation to Plaque Macrophages as a Therapeutic Strategy Targeting Atherosclerosis
Liu, H, Wu, S, Lee, H, Baudo, G, Massaro, M, Zhang, A, Hamilton, DJ & Blanco, E 2022, , advanced therapeutics, vol. 5, no. 5, 2100232. https://doi.org/10.1002/adtp.202100232

Nucleus-mitochondria positive feedback loop formed by ERK5 S496 phosphorylation-mediated poly (ADP-ribose) polymerase activation provokes persistent pro-inflammatory senescent phenotype and accelerates coronary atherosclerosis after chemo-radiation
Kotla, S, Zhang, A, Imanishi, M, Ko, KA, Lin, SH, Gi, YJ, Moczygemba, M, Isgandarova, S, Schadler, KL, Chung, C, Milgrom, SA, Banchs, J, Yusuf, SW, Amaya, DN, Guo, H, Thomas, TN, Shen, YH, Deswal, A, Herrmann, J, Kleinerman, ES, Entman, ML, Cooke, JP, Schifitto, G, Maggirwar, SB, McBeath, E, Gupte, AA, Krishnan, S, Patel, ZS, Yoon, Y, Burks, JK, Fujiwara, K, Brookes, PS, Le, N-T, Hamilton, DJ & Abe, J-I 2021, , Redox Biology, vol. 47, 102132, pp. 102132. https://doi.org/10.1016/j.redox.2021.102132

EpCAM-Targeting Aptamer Radiotracer for Tumor-Specific PET Imaging
Li, F, Zeng, Z, Hamilton, D, Zu, Y & Li, Z 2021, , Bioconjugate chemistry, vol. 32, no. 6, pp. 1139-1145. https://doi.org/10.1021/acs.bioconjchem.1c00188

Plumbagin elicits cell-specific cytotoxic effects and metabolic responses in melanoma cells
Zhang, H, Zhang, A, Gupte, AA & Hamilton, DJ 2021, , Pharmaceutics, vol. 13, no. 5, 706. https://doi.org/10.3390/pharmaceutics13050706

Structure-Based Design of a Selective Class I Histone Deacetylase (HDAC) Near-Infrared (NIR) Probe for Epigenetic Regulation Detection in Triple-Negative Breast Cancer (TNBC)
Zhang, K, Liu, Z, Yao, Y, Qiu, Y, Li, F, Chen, D, Hamilton, DJ, Li, Z & Jiang, S 2021, , Journal of Medicinal Chemistry, vol. 64, no. 7, pp. 4020-4033. https://doi.org/10.1021/acs.jmedchem.0c02161

64Cu/177Lu-DOTA-diZD, a Small-Molecule-Based Theranostic Pair for Triple-Negative Breast Cancer
Huang, Y, Yang, Z, Li, F, Zhao, H, Li, C, Yu, N, Hamilton, DJ & Li, Z 2021, , Journal of Medicinal Chemistry, vol. 64, no. 5, pp. 2705-2713. https://doi.org/10.1021/acs.jmedchem.0c01957

Management of primary cardiac paraganglioma
Chan, EY, Ali, A, Umana, JP, Nguyen, DT, Hamilton, DJ, Graviss, EA, Ravi, V, MacGillivray, TE & Reardon, MJ 2020, , The Journal of thoracic and cardiovascular surgery. https://doi.org/10.1016/j.jtcvs.2020.09.100

Stress-induced premature aging mediated by mitochoindrial hibernation promotes atherosclerosis
Kotla, S, Zhang, A, Imanishi, M, Ae Ko, K, Lin, S, Gi, Y, Fujiwara, K, Burks, JK, Le, N-T, Hamilton, DJ & Abe, JI 2020, , The 21st International Vascular Biology Meeting, 9/9/20 - 9/12/20.

Poly (adp-ribose) Polymerase (parp) Activation and Mitochondrial Hibernation Induced by P90rsk-mediated Erk5 S496 Phosphorylation Promote Mitochondrial Ros Production in Macrophage
Kotla, S, Zhang, A, Ae Ko, K, Imanishi, M, Fujiwara, K, Yoon, Y, Brooks, P, Hamilton, DJ & Abe, JI 2020, , Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 40, no. Sippl_1, 336, pp. A336.

Discovery of class i histone deacetylase inhibitors based on romidpesin with promising selectivity for cancer cells
Zhang, K, Yao, Y, Tu, Z, Liao, C, Wang, Z, Qiu, Y, Chen, D, Hamilton, DJ, Li, Z & Jiang, S 2020, , Future Medicinal Chemistry, vol. 12, no. 4, pp. 311-323. https://doi.org/10.4155/fmc-2019-0290

Time-dependent replicative senescence vs. disturbed flow-induced pre-mature aging in atherosclerosis
Dominic, A, Banerjee, P, Hamilton, DJ, Le, N-T & Abe, JI 2020, , Redox Biology, vol. 37, 101614. https://doi.org/10.1016/j.redox.2020.101614

The effect of plumbagin on progression feature and bioenergetic function in melanoma with different aggressiveness
Zhang, H, Zhang, A, Gupte, AA & Hamilton, DJ 2020, , 2020 MAPTAs 3rd Annual Summer Science Symposium, 9/2/20 - 9/3/20.

Mitochondria and chronic effects of cancer therapeutics: The clinical implications
Dominic, A, Hamilton, D & Abe, JI 2021, , Journal of Thrombosis and Thrombolysis, vol. 51, no. 4, pp. 884-889. https://doi.org/10.1007/s11239-020-02313-2

Cancer Treatment (CTCT) Promotes Oxidative Stress and Alters Monocyte/ macrophage Biology
Kotla, S, Zhang, A, Ae Ko, K, Imanishi, M, Mazhar, H, Thomas, T, Gi, Y, Vu, HT, Krishnan, S, McBeath, E, Lin, S, Kleinerman, E, Schadler, K, Fujiwara, K, Gupte, AA, Le, N-T, Hamilton, DJ & Abe, JI 2019, , Free Radical Biology and Medicine, vol. 145, no. S1, pp. S134.

Discovery of class i histone deacetylase inhibitors based on romidpesin with promising selectivity for cancer cells
Zhang, K, Yao, Y, Tu, Z, Liao, C, Wang, Z, Qiu, Y, Chen, D, Hamilton, DJ, Li, Z & Jiang, S 2020, , Future Medicinal Chemistry, vol. 12, no. 4, pp. 311-323. https://doi.org/10.4155/fmc-2019-0290

Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical
Yang, Z, Li, F, Yelamanchili, D, Zeng, Z, Rosales, C, Youker, KA, Shen, H, Ferrari, M, Mahmarian, J, Pownall, HJ, Hamilton, DJ & Li, Z 2019, , advanced therapeutics, vol. 2, no. 8. https://doi.org/10.1002/adtp.201900005

The Role of Estrogen in Protection of Skeletal Muscle Function in Diastolic Dysfunction
Chatterjee, S, Li, S, Zhang, A, Vedula, I, AlRukby, J, Hamilton, DJ & Gupte, AA 2019, , Circulation Research, vol. 125.

Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment
Ma, X, Bi, E, Lu, Y, Su, P, Huang, C, Liu, L, Wang, Q, Yang, M, Kalady, MF, Qian, J, Zhang, A, Gupte, AA, Hamilton, DJ, Zheng, C & Yi, Q 2019, , Cell Metabolism, vol. 30, no. 1, pp. 143-156.e5. https://doi.org/10.1016/j.cmet.2019.04.002

Single-Molecule Force Measurement Guides the Design of Multivalent Ligands with Picomolar Affinity
Yang, Z, Jiang, S, Li, F, Qiu, Y, Gu, J, Pettigrew, RI, Ferrari, M, Hamilton, DJ & Li, Z 2019, , Angewandte Chemie - International Edition, vol. 58, no. 16, pp. 5272-5276. https://doi.org/10.1002/anie.201814347