Basic Science and Translational Research
Smoking causes the two most lethal lung diseases, lung cancer and COPD. One of the major mysteries of the smoking link to these two lung diseases is the fact that many, indeed most smokers, do not develop either disease. Our group is concerned with mechanisms by which some individuals protect themselves from the harmful effects of smoking, with developing diagnostic and risk-assessment tools for the early detection of lung cancer, in developing new approaches to understanding the mechanisms by which these diseases arise and, in the case of lung cancer, spread beyond the lung, and with using genomic and molecular tools to define new approaches to treatment of lung cancer and COPD.
Avi Spira leads a Bioinformatics group that uses new and existing statistical and computational methods to analyze large data sets of gene expression in lung epithelial cells and lung tumors, in order to discover new diagnostic tools, new insights into cancer and COPD pathogenesis, and new approaches to treatment of these diseases. The Bioinformatics group involves graduate students from the University-wide program in Bioinformatics, and collaborations with faculty such as Jim Collins in the College of Engineering at Boston University, and involves collaborations with other institutions.
Katrina Steiling’s research focuses on applying high-throughput genomic tools and emerging computational methods to develop improved diagnostics, prognostics, and risk stratification tools for phenotypically complex lung diseases such as COPD and lung cancer. Dr. Steiling’s primary research involves gene expression profiling of the airway epithelium from individuals with COPD in order to understand the molecular mechanisms of this disease and its relationship to lung cancer. She has also worked to apply airway gene expression profiling to the diagnosis of lung cancer, to understand the relationship between smoking-induced changes in gene expression in the bronchial airway and the upper airway, and to elucidate the relationship between smoking-induced changes in airway gene and protein expression.
Hasmeena Kathuria is studying the molecular events involved in the transition from early lung tumors to metastases, the genes involved and their function and regulation. She is particularly interested in how the ETS family of transcription factors and target genes such as Twist1 participate in EMT and lung carcinogenesis. We are also interested in the relation between molecular mechanisms that regulate cellular events during lung development that are also involved in the dysregulation of cell proliferation and differentiation and angiogenesis that characterizes lung cancer. As an example, along with Drs. Yuxia Cao, Jining Lu, and Maria I Ramirez, we are studying lncRNAs and microRNAs, which have recently been discovered as a new mechanism for controlling levels of expression of genes, that are involved in development but also appear to be involved in the regulation of important oncogenes and tumor suppressor genes in cancer. Frank Schembri and Avi Spira are presently exploring the levels of microRNA expression in airway epithelial cells of smokers with and without cancer and are computationally determining which genes these microRNAs might regulate.
Our work on smoking and COPD centers on the causal role cigarette smoking plays in the pathogenesis of COPD and the importance of intra-pulmonary anti-oxidant defenses in protecting against smoking-induced lung inflammation. In collaboration with Drs. Stephen Lam, Jim Hogg, Peter Pare and Don Sin at the University of British Columbia, we are currently exploring whole-genome mRNA and microRNA changes in the airways and lungs of smokers with COPD in order to to better understand the molecular diversity of COPD both for developing subtype-targeted therapies and biomarkers that would allow for more biologically relevant diagnosis. Additionally, using a unique cohort of lung tissues with existing whole genome-expression and genotyping data, we will identify genetic variants that influence these airway gene expression changes and may ultimately serve as markers of disease susceptibility and progression.
It is clear from the above that our experimental approaches are varied and involve the tools of genomics and proteomics, bioinformatics, molecular biology, methods for studying regulation of gene expression, new tools for inserting genes into cells, and employ animal models of disease as well as studies of human subjects (translational research). Some of our work is supported by R01 and K08-type grants, or by a Program Project in lung development, some are supported by industry, and a number of investigators are involved in a NHLBI-sponsored R01 to investigate molecular phenotypes of lung disease. Many of the members of the Lung Cancer/COPD group also participate in the Epithelial, Lung Development Group, Stem Cell Group, and in the Bioinformatics Group.
- Jerome S Brody, MD
- Avrum Spira, MD, MSc
- Katrina Steiling, MD, MSc
- Marc Lenburg, PhD
- Jennifer Beane, PhD
- Catalina Perdomo, PhD
- Adam Gower, PhD
- Christina Anderlind, MD
- Hasmeena Kathuria, MD
- Maria I. Ramirez, PhD
- Yuxia Cao, MD
- Darrell Kotton, MD
- Martin Joyce-Brady, MD
- Frank Schembri, MD
- Jining Lu, PhD
- Gang Liu, PhD
- Paola Sebastiani, PhD
- Daniel Brooks, MPH, DSc
- Yuriy Aleksevev, PhD
- Joshua Campbell, MD
- Charles Dumont, MD
- Ali Jiwani, MD
- John Brothers (PhD student, Bioinformatics)
- Joseph Gerrein (PhD student, Bioinformatics)
- Becky Kusko (PhD student, Genetics and Genomics)
- Kahkeshan Hijazi (PhD student, Bioinformatics)
- Ania Tassinari (PhD student, Bioinformatics)
- Teresa Wang (PhD student, Bioinformatics)
- Carly Garrison (PhD student, Genetics and Genomics)
- Martine Dumas, MPH, RN
- Sherry Zhang
- Hanqiao Luo
- Huiqing Si
- Eduard Drizik
- Ji Xiao
- Emma Chu
- Avi Spira
- Katrina Steiling
- Hasmeena Kathuria,
- Marty Joyce Brady
- Jerry Brody
- Darrell Kotton
- Jining Lu
Clinical and Health Services Research
In addition to our basic science and translational research, we have several on-going patient-oriented research projects related to care of lung cancer patients.
Renda Wiener’s research focuses on understanding how having a potentially malignant pulmonary nodule detected and evaluated for lung cancer affects patients, their families, and the health care system. Through qualitative research and surveys with patients with a pulmonary nodule and the physicians who care for them, we have learned that many patients overestimate their risk of lung cancer and experience substantial anxiety related to the uncertainty of an indeterminate pulmonary nodule, a fact that is under-recognized by physicians and often not addressed during typical doctor-patient communication about the nodule. Dr. Wiener and her collaborators are working to develop tools to support patient-centered, shared decision-making for patients with a pulmonary nodule. Meanwhile, we are also studying the effects of pulmonary nodule evaluation on the healthcare system. We have learned that evaluation varies tremendously at different medical centers and is often not evidence-based. Finally, Dr. Wiener is now embarking on research to study implementation of lung cancer screening in the VA system, including unanticipated challenges.
- Wiener RS, Gould MK, Woloshin S, Schwartz LM, Clark JA. “The thing is not knowing”: Patients’ perspectives on surveillance of an indeterminate pulmonary nodule. Heatlh Expectations. 2012; in press.
- Wiener RS, Gould MK, Woloshin S, Schwartz LM, Clark JA. “What do you mean, a spot?”: A qualitative analysis of patients’ reactions to discussions with their doctors about pulmonary nodules. Chest. 2012 Jul 17. doi: 10.1378/chest.12-1095. [Epub ahead of print].
- Slatore CG, Cecere LM, LeTourneau J, O’Neil ME, Duckart JP, Wiener RS, Farjah F, Cooke CR. Intensive care unit outcomes among patients with lung cancer in the SEER-Medicare registry. J Clin Oncol. 2012;30(14):1686-91.
- Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: An analysis of discharge records. Ann Intern Med. 2011;155(3):137-44.
- Renda Soylemez Wiener, MD
- Melissa Tukey, MD: Procedure utilization