About the Lab
Our research interests focus on defining how dietary fats alter immune function and the resulting impact on disease pathogenesis. Unresolved tissue damage is a hallmark of intestinal diseases, including inflammatory bowel disease (IBD). Macrophage anti-inflammatory and pro-tissue repair functions are essential to the repair of tissue damage, and loss of these functions can result in increased pathology in intestinal diseases such as IBD. High-fat diets (HFD) are associated with increased pathology in many inflammatory diseases, including IBD.
HFDs can exacerbate intestinal pathology and are well known to alter macrophage anti-inflammatory functions. However, the role of HFDs in impairing macrophage tissue repair functions in response to intestinal damage is less understood. We seek to understand the role of HFDs in modulating macrophage tissue repair functions in response to intestinal damage and the resulting impact on the resolution of tissue damage in inflammatory bowel disease and other intestinal diseases.
Primary Investigator
Define the impact of HFDs on macrophage clearance of apoptotic neutrophils in response to intestinal damage.
Macrophage recognition of apoptotic neutrophils is key to their production of pro-tissue repair responses to tissue injury. Using mouse models and in vitro studies, we seek to understand how HFDs impact macrophage pro-tissue repair functions in response to damage stimuli such as apoptotic neutrophils.
Define the impact of HFD on human macrophage responses to intestinal injury in a human intestinal epithelial-macrophage co-culture system.
Human macrophage recognition of apoptotic neutrophils is key to the inductions of tissue repair functions. Using a novel human enteroid-macrophage co-culture system, we seek to understand how HFDs impact macrophage pro-tissue repair functions of human macrophages and the resulting impact on intestinal epithelial healing.
Determine the impact of unsaturated and saturated fatty acids on macrophage responses to apoptotic neutrophils and the impact intestinal epithelial healing.
The lipid composition of HFD is complex, and it is critical to understand how the overall diet composition and specific lipid components impact intestinal repair. We seek to define how specific lipid components of the diet affect macrophage responses to intestinal damage signals.
Emily K. Anderson, Andrea A. Hill and Alyssa H. Hasty. Stearic Acid Accumulation in Macrophages Induces Toll-Like Receptor 4/2-Independent Inflammation Leading to Endoplasmic Reticulum Stress–Mediated Apoptosis. Atherosclerosis, Thrombosis, and Vascular Biology. 2012, Jul;32(7):1687-95. PubMed PMID: 22556332.
Arion J. Kennedy, Corey D. Webb, Andrea A Hill, Marnie L Gruen , Laurel G Jackson and Alyssa H Hasty. Loss of CCR5 results in glucose intolerance in diet-induced obese mice. American Journal of Physiology. 2013, Oct 1;305(7):E897-906. PubMed PMID: 23941876.
Andrea A. Hill, Reid Bolus and Alyssa Hasty. A Decade of Progress in Adipose Tissue Macrophage Biology. Immunological Reviews. 2014, Nov;262(1):134-52. PubMed PMID: 25319332.
Andrea A. Hill and Emily Anderson-Baucum, Corey D.Webb, Arion Kennedy and Alyssa Hasty. Activation of NF-κB drives the enhanced survival of adipose tissue macrophages in an obesogenic environment. Molecular Metabolism. 2015, Oct;4(10):665-77. PubMed PMID: 26779432.
Andrea A. Hill and Gretchen E. Diehl. The Infectious Cause of the Chronic Effect. Cell Host Microbe Previews. 2015 Oct 14;18(4):383-5. PubMed PMID: 26468738.
Jeb S. Orr, Arion J. Kennedy, Andrea A. Hill, Emily K. Anderson-Baucum, Merla J. Hubler and Alyssa Hasty. CC-chemokine receptor 7 (CCR7) deficiency alters adipose tissue leukocyte populations in mice. Physiological reports. 2016 Sep;4(18). PubMed PMID: 27655794.
Ran You, Francesco J. DeMayo, Jian Liu, Sung-Nam Cho, Bryan M. Burt, Chad J. Creighton, Roberto F. Casal, Donald R. Lazarus, Wen Lu, Hui-Ying Tung, Xiaoyi Yuan, Andrea Hill-McAlester, Myunghoo Kim, Sarah Perusich, Loraine Cornwell, Daniel Rosen, Lizhen Song, Silke Paust, Gretchen Diehl, David Corry and Farrah Kheradmand. IL17A Regulates Tumor Latency and Metastasis in Lung Adeno and Squamous SQ.2b and AD.1 Cancer. Cancer Immunol Res. 2018 Jun;6(6):645-657. Epub 2018 Apr 13. PubMed PMID: 29653981.
Myunghoo Kim*, Carolina Galan*, Andrea A. Hill*, Wan-Jung Wu, Hannah Fehlner-Peach, Deborah Schady, Matthew L. Bettini, Kenneth W. Simpson, Randy S. Longman, Dan R. Littman, Gretchen E. Diehl. Critical role for the microbiota in CX3CR1+ intestinal mononuclear phagocyte regulation of intestinal T cell responses. *Authors contributed equally to this work. Immunity. 2018 Jul 17;49(1):151-163.e5. PubMed PMID: 29980437.
Andrea A. Hill and Gretchen E. Diehl. Identifying the Patterns of Pattern Recognition Receptors. Immunity Previews. 2018 Sep18;49(3):389-391. PubMed PMID: 30231979.
Myunghoo Kim, Andrea A. Hill, Wan-Jung Wu &Gretchen E. Diehl. Intestinal microbes direct CX3CR1+ cells to balance intestinal immunity. Gut Microbes, 2019. doi: 10.1080/19490976.2018.1559683.
Myunghoo Kim, Bonhee Gu, Matthew C. Madison, Hyo Won Song, Kendra Norwood, Andrea A. Hill, David Corry, Farrah Kheradmand, Gretchen E. Diehl. Cigarette smoke induces intestinal inflammation via a Th17 cell-neutrophil axis. Frontiers in Immunology.2019;10:75. eCollection 2019. PubMed PMID: 30761142.
Daniel F. Zegarra-Ruiz, Dasom V. Kim, Kendra Norwood, Myunghoo Kim, Wan-Jung H. Wu, Fatima B. Saldana-Morales, Andrea A. Hill, Shubhabrata Majumdar, Stephanie Orozco, Rickesha Bell, June L. Round, Randy S. Longman, Takeshi Egawa, Matthew L. Bettini and Gretchen E. Diehl. 2021. Thymic development of gut-microbiota-specific T cells. Nature. doi: 10.1038/s41586-021-03531-1.
Andrea A. Hill*, Myunghoo Kim*, Daniel F. Zegarra-Ruiz, Hyo Won Song, Angela M. Major, Michael C. Renfroe, Wan-Jung Wu, Kendra Norwood and Gretchen E. Diehl. Defective intestinal repair after short-term high fat diet due to loss of efferocytosis. Under Revision. *Authors contributed equally to this work. doi: https://doi.org/10.1101/790220.
McAlester Lab
Baylor College of Medicine
Department of Pathology and Immunology
One Baylor Plaza, Debakey M904, Houston, TX 77030
Phone: 713-798-1738
Email: andrea.mcalester@bcm.edu