As an Assistant Professor of Biochemistry and Physiology with a specialized focus on the developmental origins of metabolic diseases, I lead innovative research at the intersection of maternal metabolism, breastmilk composition, childhood obesity protection, and obesity resistance in adulthood. My research investigates how obesity's roots in early childhood not only predispose individuals to immediate health risks but also set the stage for metabolic complications traditionally associated with adulthood.
My Lab is at the forefront of uncovering how the developmental programming of adipose tissue and immune cells during infancy and childhood influences metabolic health and obesity resistance in later life. Our work begins to uncover the complex relationship between adipose tissue development and immune cell programming. By focusing on both the early-life and lifelong implications of metabolic programming, my research revealed a crucial link between the quality of maternal dietary fatty acids, the composition of breastmilk, and the offspring responses in metabolic tissues as we age. Our interdisciplinary approach, blending physiology, cellular and molecular biology, as well as basic and clinical research, enables us to tackle many complex questions that seek to address the root causes of obesity and metabolic diseases from infancy through adulthood.
A major unanswered question in the field is in the persistence of adipose and immune cell programming for later-life obesity risk. We apply pioneering techniques in single-cell RNA sequencing, epigenetics, cellular and mitochondrial metabolism, and whole animal energy balance. We developed isolation of adipocyte stem-like cells and adipose tissue immune cells in mouse pups and adult mice to begin to understand the mechanistic drivers. In partnership with clinical researchers, my work bridges the gap between basic science and translational interventions, aiming to develop targeted ways to mitigate obesity and metabolic diseases, such as maternal exercise. Here, we investigate the benefit that maternal activity has on milk fat and bioactives quality, differential milk-derived cell populations, and ultimately on infant metabolism. Connecting the causal chain from mother’s milk to infant to outcome, we employ a state-of-the-art infant metabolic phenotyping system that captures infant metabolic rate to understand their fuel utilization. Importantly, we model our clinical observations in the mouse using our rodent indirect calorimeter to investigate the early-life setting.
My research goals are to advance our understanding of the molecular basis of obesity and pave the way for innovative treatments and preventive measures, reflecting my commitment to combatting this global health challenge. Driven by a passion for transformative research, technology, and a concern for public health, I continue to seek out new horizons in the fight against obesity and metabolic diseases.
Clinical/Research Interests:
- Maternal metabolic health, breastmilk signaling lipid composition, and infant energy expenditure
- Adipose tissue development, biology, and metabolism
- Epigenetic regulation of metabolic programming in adipocytes
- Physiology of lipid biology and mechanisms, especially early in life
Funding:
Pending –
Isganaitis, Rudolph, Fields (Multi-PI)
Title: Maternal exercise during lactation to ignite infant metabolism
Grant Number (if applicable): R01 HD117197-01
Sponsor: NICHD
Start Date: 09/01/2024; End Date: 08/31/2029
Presbyterian Health Foundation Bridge Fund (Rudolph, PI) 10/01/2024 – 09/30/2025
NR2F2 Pioneers Neonatal Beige Adipogenesis to Protect Against Later-life Obesity
Our PHF Bridge Fund application is in response to the R01-A1 (31st percentile) critiques and subsequent discussion with my NIH program officer. PHF Bridge Funds requested will address scientific issues raised in our R01 critiques, generate essential preliminary data, and maintain essential laboratory functions.
College of Medicine Alumni Association (Rudolph, PI) 07/01/2024 – 06/30/2025
Proinflammatory fatty acids poise neonatal immune cells for triggering obesity-prone adipocyte formation
Our COMAA project aims to identify the specific macrophage inflammatory signals that cause adipocytes to preferentially store fat, setting the stage for childhood obesity risk.
Oklahoma Center for Adult Stem Cell Research (Rudolph, PI) 01/01/2024 – 12/31/2024
NR2F2 establishes fat-burning adipocytes for later-life obesity protection
Our proposal investigates how pro-inflammatory fatty acids exposures early in life program fat tissues metabolism, growth, and responses to excessive food intake. We identified a key metabolic transcription factor that is suppressed by omega-6 fatty acid exposures. We investigate how NR2F2 establishes nutrient-burning beige adipocytes in the neonatal mouse by identifying the genes, pathways, DNA binding sites, and interacting proteins in both adipocyte stem-like cells and the adipocytes they become.
R01 DK131064 (Li, Tiangang, Rudolph Co-I) 01/01/2022 - 12/31/2025
Sulfur Amino Acid Metabolism and Regulation of Hepatic Metabolic Flexibility
This study aims to understand how altered sulfur amino acid metabolism contributes to liver fat accumulation and inflammation in fatty liver disease. In addition, this study investigates the mechanisms regulating hepatic sulfur amino acid metabolism and if they serve as potential therapeutic targets for treating fatty liver disease.
R01 AR076938 (Horsley, PI; Rudolph site-PI) 12/1/2019 – 11/31/2024
Mechanism and impact of Intradermal adipocyte remodeling in skin fibrosis
Understanding how mature adipocytes are impacted by fibrosis development and contribute to skin fibrosis will give us new insights into the basic biology of fibrosis development and may lead to novel molecular and cellular therapies for fibrosis conditions.
Select Publications:
- Hill K, Mullen GP, Nagareddy P, Zimmerman K, Rudolph MC. Key Questions and Gaps in Understanding Adipose Tissue Macrophages and Early-Life Metabolic Programming. Am J Physiol Endocrinol Metab. 2024 Aug 22;. doi: 10.1152/ajpendo.00140.2024. [Epub ahead of print] Review. PubMed PMID: 39171752.
- Das S, Mukhuty A, Mullen GP, Rudolph MC. Adipocyte Mitochondria: Deciphering Energetic Functions across Fat Depots in Obesity and Type 2 Diabetes. Int J Mol Sci. 2024 Jun 18;25(12). doi: 10.3390/ijms25126681. Review. PubMed PMID: 38928386.
- Neville MC, Demerath EW, Hahn-Holbrook J, Hovey RC, Martin-Carli J, McGuire MA, Newton ER, Rasmussen KM, Rudolph MC, Raiten DJ. Parental factors that impact the ecology of human mammary development, milk secretion, and milk composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 1. Am J Clin Nutr. 2023 Apr;117 Suppl 1(Suppl 1):S11-S27. doi: 10.1016/j.ajcnut.2022.11.026. PubMed PMID: 37173058.
- Varshney R, Das S, Trahan GD, Farriester JW, Mullen GP, Kyere-Davies G, Presby DM, Houck JA, Webb PG, Dzieciatkowska M, Jones KL, Rodeheffer MS, Friedman JE, MacLean PS, Rudolph MC. Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors. iScience. 2023 Jan 20;26(1):105750. doi: 10.1016/j.isci.2022.105750. eCollection 2023 Jan 20. PubMed PMID: 36590177
- Wolfs D, Lynes MD, Tseng YH, Pierce S, Bussberg V, Darkwah A, Tolstikov V, Narain NR, Rudolph MC, Kiebish MA, Demerath EW, Fields DA, Isganaitis E. Brown Fat-Activating Lipokine 12,13-diHOME in Human Milk Is Associated With Infant Adiposity. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e943-e956. doi: 10.1210/clinem/dgaa799. PubMed PMID: 33135728; PubMed Central PMCID: PMC7823229.
Complete Bibliography:
https://www.ncbi.nlm.nih.gov/myncbi/michael.rudolph.2/bibliography/public/