Research

Faculty Research Interests

Marta Bueno Fernandez, PhD

Idiopathic Pulmonary Fibrosis (IPF) is a fatal and progressive lung disease, characterized by progressive scarring of the lung. IPF prevalence dramatically increases with age, and aging is a known risk factor for IPF. However, there is limited understanding in the mechanisms involved in the increased vulnerability of the aging lung to develop lung fibrosis. Under Dr Mora’s mentoring, Dr Bueno’s published findings were pioneered to identify alterations in mitochondrial homeostasis in the aging type alveolar epithelial cell (AECII) as a critical component of the pathogenesis of IPF. Currently, our studies are extending to other diseases characterized by abnormal tissue repair and exaggerated remodeling, including pulmonary hypertension (PH).

Beibei “Bill” Chen, PhD

Dr. Chen’s primary research interest involves the study of the molecular mechanisms that control inflammation and cell proliferation via protein ubiquitination. He has identified and characterized more than 10 novel ubiquitin E3 ligases over the last four years. These works have been published in top-tier journals, including Nature Immunology, Nature Medicine, Cell Reports, Science Translational Medicine, and the Journal of Experimental Medicine. Dr. Chen’s second area of research focus is small molecule drug design. Over the past two years, he has submitted 10 provisional patents related to novel anti-inflammatory/cancer compounds. In addition, he has successfully designed and synthesized a novel series of first-in-class small molecule FBXO3 protein inhibitors. One of his lead compounds, BC-1261, has passed preclinical PK/toxicity studies and was discussed at an FDA pre-IND meeting in May 2015. Recently, he has also designed a novel series of potent, selective PDE4, HECTD2, StamBP, Fbxo7, Fbxo48, FIEL1, DCN1 inhibitors that exhibit excellent activities in vivo. His long-term goal is to develop a new class of therapeutics that combat cancer and inflammatory diseases by focusing on novel mechanisms.

Yvonne Eisele, PhD

Dr. Eisele is an expert in age-related protein aggregation diseases like Alzheimer’s disease, Parkinson’s disease, and transthyretin amyloidosis. By characterizing pathogenic protein aggregates and delineating the molecular and cellular changes they elicit in affected tissue, her goal is to identify novel biomarkers and therapeutic targets. The Eisele lab collaborates closely with the clinical team at the recently founded Cardiac Amyloidosis Center at the University of Pittsburgh and UPMC, and is dedicated to translating basic research findings to benefits for patients.

Toren Finkel, MD, PhD

Toren Finkel is a physician-scientist renowned for his research on the basic science of aging. He is the Director of the UPMC-University of Pittsburgh Aging Institute and a Professor of Medicine in the Pitt Department of Medicine’s Division of Cardiology. For over twenty years, his research group has focused on issues involved in mitochondrial function, cellular metabolism, oxidative stress, and aging. Due to the wide span of  biological interests, his lab has developed expertise in mitochondrial assays, cell and molecular biology approaches, and the generation of mouse models along with whole animal physiological measurements. A long-term goal is to uncover the molecular basis of mammalian aging and age-related diseases through the study of  different cellular pathways, including stem cell self-renewal, reactive oxygen species, sirtuins, autophagy, mTOR signaling and mitochondrial metabolism.  A particular focus in the last several years has been the role that a decline in autophagy might phenocopy vascular aging. His lab has also developed novel strategies to measure mitophagy in vivo.

Daniel Forman, MD

A Professor of Medicine, Dr. Forman is dually trained in geriatrics and cardiology. He holds appointments in both Divisions at UPMC as well as in both the Geriatrics Research Education and Clinical Center (GRECC) and the Cardiology Division at the Pittsburgh VA. With NIH funding, he is studying the benefit of nitrate capsules for fatigue and function in older adults with heart failure and preserved ejection fraction. In two other NIH projects, he is studying the impact of exercise on skeletal muscle gene transcription (Molecular Transducers of Physical Activity in Humans [MoTrPAC]), and the impact of exercise training on cognition (Investigating Gains in Neurocognition in an Intervention Trial of Exercise [IGNITE]). At the VA, he is comparing the impact of different training regimens (strength, aerobic, and inspiratory muscle training) on skeletal muscle morphology, gene expression, and functional capacity. He is also researching the utility of prehabilitation in frail elderly prior to abdominal and cardiothoracic surgery. Finally, Dr. Forman is funded by PCORI to devise novel strategies to improve cardiac rehabilitation, especially methods to improve enrollment, adherence, and value for complex, older cardiovascular patients.

Aditi Gurkar, PhD

An Assistant Professor of Medicine, Dr. Gurkar’s interest is in understanding the role of DNA damage in aging and age‐related diseases. Her lab’s long-term goal is to uncover DNA damage induced metabolic re-programming that drives these aging pathologies. Her NIH‐funded research focuses on identifying the nucleo-mitochondrial communication signaling in response to endogenous DNA damage. Additionally, the lab is very interested in identifying cellular responses to genotoxic stress, especially in post-mitotic tissues such as the heart and brain. By defining these molecular mechanism(s), she hopes to identify novel therapeutic targets that can be exploited to extend healthspan.

Gang Li, PhD

The primary research focus of Dr. Gang Li’s lab is to understand the molecular mechanisms underlying the contribution of disease-associated, non-coding functional SNPs in aging-related diseases, such as neurodegenerative disorders, cardiovascular diseases and cancers. Dr. Li’s lab has developed multiple techniques such as SNP-seq and FREP-MS to identify the causal SNPs as well as the SNP-bound regulatory proteins based on genome wide association studies (GWAS). The lab’s goal is to use human genetics (GWAS) as a guide to identify new drug targets and ultimately, to apply these findings to develop allele-specific precision drugs for aging-related human diseases as well as other diseases.

Jie Liu, PhD

Dr. Jie Liu’s research interests include the study of mitochondrial function in the context of stem cells, growth, and metabolism; vascular biology;  and genetic imprinting of the stimulatory G protein alpha-subunit in human genetic disease psuedohypoparathryroidism type 1B.

Shihui Liu, PhD

Shihui Liu, We are using the state-of-the-art multidisciplinary approaches to uncover the basic mechanisms underlying pathogenesis of bacterial protein toxins and engineer these toxins for cancer targeted therapy. We are also interested in uncovering the underlying mechanisms of tumorigenesis and aging and translating those findings into patients. Our current research covers four areas of scientific investigations: (1) Studying the pathogenesis of anthrax toxins and other bacterial protein toxins, developing therapeutics; (2) Using genome-wide genetic approaches to identify host genes required for the actions of bacterial protein toxins, thereby revealing the mechanisms of these toxins in pathogenies; (3) Investigating RAS-RAF-MEK-ERK signaling in cancer, creating and assessing of novel engineered protein toxins and other therapeutics in targeting this pathway in tumor microenvironment; (4) exploring the physiological roles of diphthamide modification on eukaryotic translation elongation factor-2 (eEF2) in life and aging.

Yuan Liu, PhD

The ubiquitin proteasome system (UPS) is a complex, hierarchical, and regulated cellular system that dominates selective protein degradation to modulate the abundance and activity of proteins in the cell. The majority of proteins is controlled by the UPS through the ATP-dependent enzymatic cascade, including the ubiquitin activating enzyme (E1), the ubiquitin conjugating enzyme (E2), and the ubiquitin ligase (E3). Dr. Liu has a long-standing research interest in UPS, especially ubiquitin ligase E3s. Her earlier work during PhD study and postdoctoral training focused on the regulatory mechanisms of protein ubiquitylation and degradation. At ALI center, Dr. Liu’s study has expanded to ubiquitylation in mitochondrial biology, mainly in acute lung injury model. Her very recent discovery includes ubiquitin E3 ligase subunits Fbxl18 and Fbxl7 target anti-apoptotic protein survivin to modulate mitochondrial homeostasis. The Fbxl18-Fbxl7-survivin axis provides unique regulatory pathway that ubiquitin E3 modulates mitochondrial function and apoptosis, serving as therapeutic target for cancer treatment. Dr. Liu is also interested in small molecule drug development in lung disease. Collaborating with Drs. Rama Mallampalli and Bill Chen, she has developed a series of small molecule inhibitors targeting ubiquitin E3 ligases, aiming to protect mitochondrial function during acute lung inflammation and injury. Currently, they have demonstrated the potent mitochondria-protective activity of these compounds in cellular level and rodent ALI model and these works led to one provisional patent on inhibitor of ubiquitin E3 ligase neddylation and the other provisional patent application for F-box protein inhibitor.

Ana Mora, MD

Dr. Mora’s research is focused in the understanding of the pathogenesis of idiopathic Pulmonary Fibrosis (IPF), a fatal and progressive lung disease characterized by progressive scarring of the lung. IPF prevalence dramatically increases with age, and aging is a known risk factor. However, there is limited understanding of the mechanisms involved in the increased vulnerability of the aging lung to develop this disease. Mitochondrial dysfunction is a hallmark of aging, but the role of mitochondria in IPF pathobiology is unknown. Dr. Mora’s lab recently discovered that AECII from human IPF lung have accumulation of dysmorphic and dysfunctional mitochondria associated with very low expression of the crucial protective protein involved in mitochondrial homeostasis, PTEN-induced putative kinase 1 (PINK1). Low expression of PINK1 leads to increased susceptibility to cell apoptosis and fibrosis. However, no information is available on how PINK1 expression is regulated and how loss of PINK1 activates pro-fibrotic responses. Dr. Mora’s research brings forth a unique molecular model linking mitochondrial dysfunction and fibrosis that sets the stage for identifying novel links of aging and fibrosis and therapeutic targets for IPF. The lab’s studies use a combination of novel animal models with genetically altered mice and human subjects. Dr. Mora’s published findings identified alterations in mitochondrial homeostasis in the aging type alveolar epithelial cell (AECII) as a critical component of the pathogenesis of IPF. Currently, her research extends to other diseases characterized by abnormal tissue repair and exaggerated remodeling, including pulmonary hypertension (PH).

Anne Newman, MD

Dr. Newman is the Distinguished Professor and Chair of the Department of Epidemiology, with a secondary appointment as Professor of Medicine in Geriatrics. A member of NIH/NIA’s National Advisory Council on Aging, she is Principal Investigator for several large population studies and clinical trials and also serves as Director of the Center for Aging and Population Health at the Graduate School of Public Health. In addition, she collaborates with Dr. Greenspan as Co-PI of our Pepper Center, with Dr. Hanlon in the Health ABC Study, and with Dr. Nadkarni on the LIFE Study and the ENRGISE Study. Her research focuses on the factors associated with disability and healthy aging.

Shiori Sekine, PhD

Mitochondria dysfunction is associated with various diseases and aging. To maintain healthy mitochondrial network, mitochondria are equipped with several systems that can evoke appropriate stress-signaling pathways. Dr. Shiori Sekines lab is focusing on the stress-sensing mechanisms of mitochondrial proteins. Especially, she is interested in the stress-dependent regulation of mitochondrial proteases and mitochondrial import machineries. Her research goal is to provide therapeutic targets for mitochondria dysfunction-related diseases through the manipulation of stress-signaling in mitochondria.

Yusuke Sekine, PhD

Dr. Yusuke Sekine has been working on the study of molecular mechanisms underlying cellular responses to a variety of stresses such as oxidative stress, endoplasmic stress and metabolic stress. Using biochemical and cell genetic approaches, Sekine lab is currently focusing on acetyl-CoA fluctuation-dependent functional changes of organelles (including nucleoli, mitochondria and lysosomes) and activation of organelle-associated signaling pathways. A goal of the lab is to understand the sensing mechanisms of metabolite fluctuations in mammalian cells and reveal their relevance to human diseases and aging.

Bokai Zhu, PhD

Dr Zhu’s lab discovered a cell-autonomous mammalian 12h-clock that runs independently from the circadian clock to regulate 12h oscillations of gene expression and metabolism. Dr. Zhu’s lab is currently investigating the regulation as well as the physiological/pathological functions of the 12h-clock, with an emphasis on its roles in maintaining hepatic metabolic homeostasis and preventing aging-associated diseases.