Yuanpu Peter Di, PhD, MBA

The purpose of my laboratory’s research is to investigate the effects of environmental exposure on the host. We are particularly interested in infection and immunity on the lung and its associated pathophysiological response during injury, repair, and regeneration. The primary focus of my current research is the cellular and molecular actions of exposures to toxic chemicals and microorganisms that underlie the pathogenesis of chronic human diseases.

1. Lung epithelial cell phenotype, differentiation, and function upon exposure:

My laboratory provided influential identification and characterization of a novel lung epithelial cell specific, secretory protein SPLUNC1 and its roles in pulmonary diseases. The SPLUNC1-associated research has been supported by two consecutive R01 grants since 2008 including the ongoing clinical ancillary study to investigate its association with exacerbation in severe asthma. We and others have demonstrated multiple functions of SPLUNC1, including host defense, anti-inflammatory effects, a surfactant-like property, and modulation of epithelial lining fluid volume. The expression of SPLUNC1 in lung is dynamic and reflects maturational, functional, and pathological changes of lung epithelium. We are very interested in elucidating mechanisms associated with epithelial cell-mediated tissue remodeling and regeneration after recurrent bacterial and viral infection-induced injury.

2. Inflammation-associated tissue remodeling and lung tumorigenesis:

My laboratory developed and published an innovative exposure paradigm that demonstrated the synergistic effect of lung tumorigenesis (> 6 fold, p<0.0001) and higher frequency of lung tumors that harbor K-ras mutation by co-exposure of a cigarette smoke carcinogen NNK and an inflammation eliciting agent from bacteria endotoxin LPS. We have found the inflammation-associated lung tumorigenesis is differentially regulated by genders and happens with higher frequency and incidence in the females than the males. Our ongoing research effort is to understand the mechanisms and further define the roles of inflammatory mediators in the regulation of the pathogenesis associated with lung tissue remodeling and carcinogenesis after recurrent infections. Our inflammation-associated cancer model demonstrated an immunosuppressive environment that promotes T-cell exhaustion and tumorigenesis. We have also used the valuable model to determine the checkpoint blockade-based immunotherapy and generated gene signature that provided high predictive value to anti-PD1 therapeutic response in lung cancer patients. Additionally, We have a vast interest in lung stem cell biology. My lab developed mouse and human primary epithelial cell cultures for both proximal tracheal-bronchial epithelial (TBE) and distal bronchiolar epithelial (DBE) cells as excellent tools for studying effects and mechanisms of progenitor cell renewal and environment exposure. Our results revealed that intrinsic phenotypic and genotypic changes in epithelial cells can be maintained, observed, and analyzed in an ALI cell culture system and that the DBE cells may reflect pathologic changes of lung tissue remodeling and adult lung stem cell regeneration.

3. Development of novel antibiotics to overcome antimicrobial resistance (AMR):

Our effort in identifying the effects of antimicrobial milieu on host defense against respiratory infection resulted in the successful development of a next-generation peptide-based antibiotics (PAX) that demonstrate exciting and promising efficacy in overcoming multi-drug resistant (MDR) bacterial infection. New therapies for controlling MDR pathogen-induced respiratory infections are urgently needed because: (a) the mortality rate among infected individuals requiring hospitalization remains very high; and (b) overuse of antibiotics has resulted in continuing emergence of additional MDR strains with increased virulence. We have recently started two five-year R01 funding support from NIAID (as PI) and NIGMS (as Co-I with my assistant professor PI) to characterize the biological response involved in the disposition of novel antimicrobial agents, define pharmacokinetic information for the development of PAX therapy, and investigate the toxicological effects caused by therapeutic drugs. On an alternative approach in elucidating the antimicrobial resistant mechanisms associated with standard of care antibiotics and host microenvironment, we have developed novel biofilm assay to investigate bacterial adaption and evolution with analysis using whole genome sequencing (WGS) and bioinformatics. Our effort in combating AMR and developing PAX not only fills the void of lacking effective antibiotics against MDR infection but also provide a new functional model to investigate the host-pathogen interaction and determine the regenerative capacity of restoring lung epithelial cell function in preserving cell junctional integrity to protect lung from bacterial infection.

1986    National Defense Medical Center         Medicine                           Certificate      

1995    SUNY at Buffalo (Roswell Park Div.)    Biophysics                         Ph.D.              

1999    University of California at Davis            Innovation & Tech. Mgt     M.B.A.            

EOH 3210, Molecular Fundamentals

ARTSC 0130, First Experiences in Research