Since 2011, the Zachos lab has utilized human intestinal organoids to investigate host stem cell and epithelial responses to enteric pathogen (bacterial and viral) infections. In addition, the Zachos lab has developed co-culture systems that incorporate human immune cells with human organoids to interrogate mucosal immune responses to gut commensals and enteropathogens. His laboratory has demonstrated that human enteroids/colonoids functionally recapitulate normal intestinal physiology and pathophysiology of GI disorders including Inflammatory Bowel Disease, metabolic diseases (Obesity/Type II Diabetes), and pre-cancer. Using multicellular co-culture models comparing organoids from healthy subjects or diseases associated with inflammation will provide insights into disease etiology and progression ultimately leading to the development of novel treatment strategies and drug discovery.

My research is focused on understanding the cellular and molecular mechanisms by which cardiovascular risk factors, such as hypertension and blood pressure variability, increase the risk of dementia. One of my goals is to investigate the early mechanisms of autonomic and immune dysfunction to better understand the pathogenesis of cognitive impairment late in hypertension, with the goal of improving early detection of patients at risk and developing better treatment strategies to prevent cognitive decline. My laboratory studies these questions in various mouse models of hypertension utilizing interdisciplinary techniques including measurement of cerebral blood flow regulation, flow cytometry of neuroimmune populations, neurobehavioral testing, and single nuclei profiling of neuronal and glia populations.

The primary focus of our research group is the development of next-generation imaging mass spectrometry (IMS) technologies to elucidate the molecular basis of health and disease. Modern instrumentation and computing capabilities have enabled researchers to move beyond reductionist biology and, instead, probe how the components of biological entities (e.g. molecules, cells, and tissues) interact to reveal the underlying biology of disease. This systems biology approach has been accelerated by advancements in high throughput ‘omics’ technologies, however, genetic and molecular information are only part of the story. The challenge lies in understanding how these parts interact and how perturbations to the system relate to disease.

Molecular imaging effectively offers a ‘blueprint’ as to how biological components work together by providing spatial context to molecular information. From the advent of the complex microscope in the late 1600s to modern modalities such as magnetic resonance, positron emission tomography, and advanced microscopy, imaging technologies have always been at the forefront of our understanding of biochemistry and biology. However, relative to the new -omics technologies, these classical biomedical imaging technologies have limited molecular specificity. Mass spectrometry-based imaging now finds itself uniquely positioned to bridge the gap between the information rich genomics, proteomics, and metabolomics approaches and biomedical imaging technologies. IMS combines the molecular specificity of mass spectrometry with the spatial fidelity of classical histology to create molecular maps of tissues. Broadly, my research falls into two categories: (1) Developing novel mass spectrometry technologies to maximize imaging performance enabling molecular histology at cellular resolution and (2) combining imaging mass spectrometry with a variety of other biomedical imaging technologies to create new integrated modalities capable of providing a systems biology view of tissue at cellular resolution. We are applying these advanced technologies to better understand critical biomedical research areas such as Alzheimer’s, kidney, and infectious disease.

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