Yang Xiao, MBBS, PhD

Dr. Yang Xiao earned her bachelor’s degree in medicine from Peking University in China. She then moved to the United States and completed her PhD training with Dr. James Martin at Baylor College of Medicine, where she investigated the role of Hippo signaling in heart development and regeneration. Her work revealed an essential role for the Hippo pathway kinases LATS1/2 in regulating cardiac fibroblast differentiation during heart development and maintaining fibroblast quiescence in the adult heart.

Following her PhD training, Dr. Xiao joined the laboratory of Dr. Mitchell Lazar at the University of Pennsylvania for her postdoctoral training. Her research focused on transcriptional regulation in metabolic dysfunction-associated steatotic liver disease (MASLD), a hepatic manifestation of cardiometabolic disease. Through unbiased functional single-cell omics, she identified a distinct hepatocyte population that contributes to MASLD progression and characterized functional MASLD-associated GWAS variants that can predict disease susceptibility.

Dr. Xiao’s research program focuses on epigenetic regulation and interorgan communication in cardiometabolic disease. With expertise in both experimental and computational biology, her laboratory integrates unbiased genomics and proteomics with mouse genetics and human induced pluripotent stem cell models to uncover mechanisms underlying metabolic liver disease and its associated cardiac complications. Her laboratory is also interested in comparative biology, particularly how nontraditional model organisms have evolved advantageous metabolic adaptations that may inform our understanding and treatment of human disease.

Dr. Xiao’s research has received support through several awards and grants, including an American Heart Association Postdoctoral Fellowship, an NIH/NIDDK K01 Career Development Award, and a University of Pennsylvania NIDDK Digestive and Liver Center Pilot Award.

Dr. Xiao’s mentoring philosophy emphasizes individualized training that fosters scientific curiosity, critical thinking, independence, communication, and collaboration. Her goal is to prepare trainees for successful careers in biology, medicine, and related fields.

2025-2029 NIH NIDDK K01 mentored research scientist development award
2026 University of Pennsylvania NIDDK Digestive and Liver Center Pilot and Feasibility Award
2021-2023 American Heart Association Postdoctoral Fellowship
2020 Life Science Research Foundation (LSRF) postdoctoral fellowship, finalist
2020 Keystone Symposia Scholarship

In the modern society, changes in lifestyles and dietary patterns have made cardiometabolic diseases a growing global health burden. The Xiao laboratory seeks to uncover how gene-environment interactions shape the development and progression of cardiometabolic diseases through experimental and computational approaches spanning physiology, cell biology, genetics, and genomics. Our goal is to translate fundamental discoveries into strategies for the prevention, prediction, and treatment of cardiometabolic diseases.

We are interested in three major questions:
1. How do genetic variants interact with environmental and physiological cues to shape the progression of metabolic liver disease?
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a hepatic manifestation of cardiometabolic disease and affects nearly one-third of adults worldwide. Although early-stage MASLD is often reversible, a subset of patients progresses to life-threatening conditions. Understanding the factors that drive this heterogeneous progression remains a fundamental challenge. Our research examines how genetic variation interacts with environmental exposures, such as diet, and physiological stresses, including aging and inflammation, to shape MASLD progression. Our goal is to identify high-risk individuals and develop new strategies for disease prediction, prevention, and treatment.

2. How does the liver communicate with other organs in cardiometabolic disease?
Cardiometabolic disease is a systemic disorder involving complex interactions among multiple organs. The liver is not only a metabolic organ but also one of the body’s major secretory organs, producing bioactive molecules to regulate extrahepatic processes such as cardiac remodeling and blood pressure. However, how this communication is altered under cardiac and metabolic stress remains poorly understood. Our goal is to elucidate the molecular mechanisms underlying communication between the liver and other organs, providing new insights into the pathogenesis of cardiometabolic disease and identifying novel therapeutic strategies for cardiovascular disorders.

3. How do organisms with exceptional metabolic adaptations cope with metabolic stress, and can their solutions be translated to improve human health?
Numerous nontraditional model organisms have evolved remarkable strategies to withstand metabolic challenges. For example, naked mole-rats exhibit exceptional longevity and resistance to oxidative stress. Jamaican fruit bats maintain metabolic health despite chronically consuming a high-sugar diet. Our laboratory seeks to decipher the genetic and epigenetic mechanisms underlying their metabolic adaptations, with the goal of identifying new strategies to treat human metabolic diseases and promote healthy aging.

Methodologies and Techniques

• Mouse genetics - in vivo disease modeling and phenotyping
• Adeno-associated virus (AAV) and lentiviral production and in vivo delivery
• Induced pluripotent stem cell-based disease modeling
• Single-cell and spatial omics
• Functional genomics and proteomics
• Massively parallel reporter assays
• In vitro and in vivo CRISPR-based perturbation screening
• Histology, immunohistochemistry, and microscopy
• Bioinformatics, machine learning, and population genetics