Scott H Randell, PhD

Research Biosketch Links Personnel Contact

Research Interests

Figure1-1

Figure 1. X-Y plane confocal microscopy of cultured human airway epithelial cells expressing green and red fluorescent protein.

Research in Dr. Randell's laboratory is currently focused on five areas where a greater knowledge of basic cell biology can be applied towards overcoming clinical lung disease problems:

 

  1. Identification of airway epithelial stem cells. Dr. Randell's goals are to identify and isolate airway epithelial stem cells and to understand molecular mechanisms regulating airway epithelial cell proliferation and fate decisions.
  2. Micro RNA Regulation of Human Airway Epithelial Phenotype- ARRA Award. The Randell Laboratory comprehensively determines the miRNA repertoire of human airway epithelial cells will tests the ability of miRNAs to alter cell structure and function. These studies will create a valuable database and will suggest novel treatments for lung disease.
  3. Innate immunity in the airway. Dr Randell aims to better understand molecular mechanisms regulating airway epithelial adaptation to injury and chronic infection and to understand the relationship of adaptation to the pathogenesis of airway disease.
  4. Post-lung transplant ischemia reperfusion injury and bronchiolitis obliterans syndrome. The Randell Laboratory is also examining basic mechanisms of lung injury relevant to transplantation and bronchiolitis obliterans syndrome, the leading cause of lung allograft failure.
  5. Dr. Scott Randell also directs the UNC CF Center Tissue Procurement and Cell Culture Core, which provides primary and passaged human airway and alveolar epithelial cells, lung microvascular endothelial cells, media and expertise to UNC CF Center investigators and collaborators. Our facility has become a nationally and internationally recognized resource whose services are sought for collaboration, contract research, and training by academics, non-profit organizations, biotech and the pharmaceutical industry.

 

 

Figure 2-2

Figure 2. Human bronchial epithelial cells in culture, fixed with perflurocarbon OsO4 and prepared for high resolution light microscopy.

Figure 3

Figure 3. Frozen section of a human cystic fibrosis airway excised during lung transplantation, stained for mucus. Note the adhesion between the mucus in the lumen and the airway wall.

 

 

 

 

 

 

 

 

 

 

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Biographical Sketch

Scott H Randell, PhD, Associate Professor of Cell and Molecular Physiology

Education

1979: State University of NY College at New Paltz, BS, Biology.
1985: The Johns Hopkins University, Baltimore, MD, Ph.D., Toxicology/Experimental Pathology.

Professional Experience

1979-1981: Laboratory Associate, The Johns Hopkins University.
1981-1984: Medical Technologist, The Johns Hopkins Hospital.
1985-1989: Postdoctoral Fellow, Respiratory Medicine, Duke University Medical Center.
1989-1991: Staff Fellow, NIH/NIEHS.
1991-1994: Senior Staff Fellow, NIH/NIEHS.
1994-2005: Asst. Professor, Dept. of Medicine, University of North Carolina, Chapel Hill, NC.
2000-2005: Joint Appointment, Department of Cell and Molecular Physiology, UNC Chapel Hill.
2005-present: Assoc. Professor, Department of Cell and Molecular Physiology, UNC Chapel Hill.
2005-present: Joint Appointment, Dept. of Medicine, University of North Carolina, Chapel Hill, NC.

Honors and Awards

1974: New York State Regents Scholarship, 1979-Graduate Cum Laude (B.S. Degree).
1980: Scholarship from The Johns Hopkins University, 1981-Predoctoral Training Grant Recipient.
1985: Postdoctoral Training Grant Recipient.
2009: Micro RNA Regulation of Human Airway Epithelial Phenotype – ARRA Award to Randell Lab.

Greater than 30 million people in the USA suffer from respiratory diseases characterized by airway inflammation and obstruction. One of these inflammatory diseases- chronic obstructive pulmonary disease, is strongly associated with the development of lung cancer, the world’s most prevalent lethal cancer. Cells lining the airway respond to injury and are integral to the progression of lung disease and cancer development. However, many basic mechanisms regulating their function remain poorly understood. There are no specific therapies targeting disease related phenotypic changes in the airway epithelium. Micro RNAs (miRNAs) are a class of small RNA molecules known to regulate many aspects of cell behavior. Together with Drs. Scott Hammond in Cancer Cell Biology and D. Neil Hayes in Translational Medicine, the Randell Lab was awarded an ARRA RC1 Challenge grant to comprehensively determine the miRNA repertoire of human airway epithelial cells and to test the ability of specific miRNAs to alter cell structure and function. These studies will create a valuable database and will suggest novel tools to detect, monitor and treat lung cancer.

Research Support

Ongoing Research Support

1 RC1 HL 100108 (Randell/Hammond/Hayes) 9/30/09-9/29/11 NIH/NHLBI Role: Principal Investigator
Micro RNA Regulation of Human Airway Epithelial Phenotype
The major goal of this project is to gain a comprehensive understanding of the miRNA repertoire and its expression and function in hBE cells.

1 RC1 ES 018686-01 (Superfine) 9/30/09-9/29/11 NIH/NHLBI Role: Principal Investigator
Computation and Cell Culture Models for Mucus Clearance
The goal of this project is to generate computations and cell culture based models for mucus clearance - these models will have the potential to act as a sensitive assay for environmental effectors that compromise mucus height regulation, mucus rheology, cilia density and coordination.

5 P30 DK 065988-06 Boucher (PI) 4/1/09-3/31/14 NIH/NIDDK Role: Core Leader
Molecular Therapy Core Center, Core F: Cell Culture Models Core
Provide novel airway epithelial culture systems, lung microvascular endothelial cells and hepatocytes.

5 P01 HL 034322-22 Boucher (PI) 2/1/07-1/31/12 NIH/NHLBI Role: Core Leader
Pulmonary Epithelia in Health and Disease, Core C: Cell Culture Core
Support PPG projects by performing the following functions: tissue procurement, cell isolation and culture, and genetic manipulation of cell cultures.

RANDEL07XX0 Randell (PI) 7/1/07-6/30/10 CFFT Inc. Role: Principal Investigator
NDRI-UNC-CFFT Cell Resource
Receive lung tissues, process for epithelial cell harvest, characterize the cells and distribute for CF research as designated by CFFT.

R026-CR07 (Boucher) 7/1/07-6/30/11 CFF Role: Core Leader
Epithelial Function in Cystic Fibrosis, Core C
Procure tissue, characterize patients, culture cells to support research projects, develop cell lines.

Subcontract on 5 R01 HL090146-02 Stripp (PI) 9/28/07-6/30/11 Duke University/NIH/NHLBI Role: Subcontract PI
Stem Cells to Enhance Bronchiolar Reparative Capacity
Procure and analyze human lung tissues and cells to assess functional activity of stem and progenitor cells.

1R01 HL 095396-01 Knowles/Wright (PI) 9/24/08-7/31/12* NIH/NHLBI Role: Co-I
Molecular Phenotypes for Cystic Fibrosis Lung Disease
Study the role of gene expression variation in CF lung disease and the integrated analysis of SNPs/CNVs and expression data. (*support starting yr 4).

5 P01 HL 051818-15 (Samulski) 8/20/04-6/30/10* NIH/NHLBI
Gene Therapy for Cystic Fibrosis, Core B: Tissue Procurement and Cell Culture
The goal of this Core is to provide human airway tissues and cells and media to PPG investigators. These basic services are distinct from, and do not overlap with, MTCC functions related to airway cells. *7/1/09-6/30/10 is a no-cost extension.

Subcontract 104163 (Karp) 7/1/08-6/30/10 Cinc Child Hosp Med Ct(subcontract on Cystic Fibrosis Foundation grant R457-CR07, subcontract PI: Randell)
Research Development Program
The major goal of this subcontract is to provide services to the CCHMC RDP grant in isolating primary airway epithelial cells, harvesting cells, and culturing cells.

Pilot Project (Knowles) 5/1/09-4/30/10 UNC NC TRaCS Institute
Test New Drug (PTC124) to “Read-Through” Nonsense (STOP) Mutations and Correct Ciliary Function in Primary Ciliary Dyskinesia (PCD)
The major goal of this project is to test a currently available pharmacologic agent (PTC124; oral drug) in vitro as a potential treatment for nonsense (STOP) mutations in Primary Ciliary Cyskinesia (PCD), which is a recessive, genetically heterogeneous disorder of cilia.

Collaborative Funding Grant (Randell) 7/1/09-6/30/11 NC Biotech Center & Parion Sciences
The Development of Corneal and Conjunctival Epithelia Cultures for the Advancement of Novel Dry Eye Therapies
The major goals of this project are to develop primary human corneal and conjunctival epithelial cell cultures (1) to validate that ENaC plays a role in ocular fluid absorption in humans, and (2) for the development of a cell-based approach to study duration of action of multiple Parion compounds for the purpose of lead selection, with an ultimate goal of providing key insights into the biology underlying salt and fluid transport on the ocular surface.

STTR Subcontract (Flood/Egan) 8/1/09-7/31/10 TheraLogics (NIH R41 HL095293-01A2)
NF-kappa B Inhibition in Lung Ischemia-Reperfusion Injury
The major goal of this project is to determine if inhibition of NF-kappa B can ameliorate lung ischemia-reperfusion injury, a particular problem in organ transplantation.

1 R01 HL 092964-01A1 (Boucher) 1/1/10-12/31/13 NIH/NHLBI
The Role of Anaerobic Bacterial Infection in Cystic Fibrosis
The major goal of this project is to test the hypothesis that obligate anaerobic bacteria are pathogens in the CF lung and to identify when they produce this pathogenic effect.

Completed Research Support

RANDEL07P0 (Randell) 3/1/07-2/28/10 Cystic Fibrosis Foundation
Dysregulated Airway Physiology in Scnn1b Transgenic Mice
The major goal of this project is to elucidate key mechanisms by which defective mucus clearance results in chronic airway injury by: 1) studying the interaction between tethered and secreted mucins to examine mechanisms of mucus adhesion, plaque formation and airway obstruction, 2) determining causes and effects of airway inflammation and goblet cell metaplasia in Scnn1b mice, and 3) examining the pathogenesis of respiratory virus-induced airway disease in Scnn1b mice.

BOUCHE08P0 Boucher (PI) 7/1/08-6/30/09 Cystic Fibrosis Foundation Role: Co-Investigator
The Role of Anaerobic Bacterial Infection in Cystic Fibrosis
The major goal of this project is to test the hypothesis that obligate anaerobic bacteria are pathogens in the CF lung and to identify when they produce this pathogenic effect.

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Links

The UNC CF Center Tissue Procurement and Cell Culture Core

Physiology Department Profile

Center for Tobacco Regulatory Science and Lung Health

Laboratory Personnel


Dr. Scott Randell, Principal Investigator, dissecting donor tissue in the CF Center Tissue Procurement and Cell Culture Core


Leslie Fulcher,          Laboratory Manager


Ryan Snyder,  Rotation Student

YWang_TC

Yang Wang, PhD

 

 

JKim

 Jeeho Kim, Research Specialist

Zach Boggs, Research Technician

 


 

 

 

KHammond

Kelli Hammond, Research Specialist

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

         

 

 

 

 

 

 

 

 

 

Contact Information

4006 Thurston-Bowles Bldg
Campus Box #7248
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599
Phone: (919) 966-8093
Fax: (919) 966-7524
E-mail: randell@med.unc.edu

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