My early research career started with basic science work at the NIH from 1989 to 1991. Specifically, I helped to establish experimental models to measure the in-vivo effects of intravascular injected growth factors (aFGF, bFGF, and VEGF) and intravascular deliver systems for transduced endothelial cells over-expressing growth factor genes. I also used in-vitro models to predict the malignant potential of transduced endothelial cells. Once joining the BWH faculty, I continued this in-vitro work with lung cancer cell lines. I started with telomerase, and quickly expanded into adhesion molecules, exploring the activation of focal adhesion kinase following exposure of cancer cells to collagen IV matrix. This led to a series of investigations further elucidating the signal transduction pathways of this phenomenon up to the deacytelation of histones. This work led to the honor of oral presentation in the 2002 Mannick Day Award Competition for my post-doctoral fellow, Dr Nishit Mukhopadhyay.
As Director of Clinical Research of the Division of Thoracic Surgery, I oversee the quality assurance of our data collection and analysis, and mentor residents and fellows in individual research projects. My specialized biostatistics training from the Harvard School of Public Health facilitated my analysis of the Surveillance, Edidemiology, and End Results (SEER) database from the NCI, which includes over 100,000 lung cancer entries. I have used this database to generate hypotheses, which are then tested in our more complete Divisional database. Furthermore, I have trained residents in the analysis of these large databases, creating a cadre of resident researchers interested in this line of investigation. The use of SEER data to analyze the competitive outcomes of wedge resection versus lobectomy in patients over the age of 75 won the Alfred Soffer Research Award for the best abstract presented at Chest 2001. The use of SEER data to analyze the influence of primary tumor diameter on long-term survival was a runner-up abstract in the same competition the following year.
I have organized, written, conducted, and analyzed randomized prospective clinical trials. In the field of minimally invasive staging of lung cancer, I am the principal investigator of a recently closed multi-institutional phase II trial (CALGB protocol # 39803) using a video-thoracoscopic to restage mediastinal nodes following chemoradiation for stage IIIA(N2) NSCLC. This was a positive trial, presented at ASCO 2005. In regards to advanced lung cancer, I am also the principal investigator of a recently closed Dana Farber institutional trial (DFCI protocol # 96-100) combining extrapleural pneumonectomy with chemoradiation for the treatment of stage IIIB NSCLC with malignant pleural effusion. In minimally invasive surgical treatment of elderly lung cancer patients, I am the principal investigator of DFCI protocol # 02-225, a prospective study of the functional impairment and time to recovery of elderly patients undergoing thoracic surgery. Most recently, with the assistance of the CALGB Thoracic Surgery Subcommittee and the Cancer in the Elderly Committee I have written new prospective multi-institutional registry protocol (CALGB protocol # 1408010 to quantify the morbidity, mortality, functional impairment, and time to recovery of very elderly patients (over the age of 70 years) undergoing thoracic surgical procedures. This protocol has been approved by the CALGB Executive Committee and is seeking independent funding through an NIH grant.
I believe my most significant contributions to the Thoracic Surgical literature to date include: analysis of the role of repeat operations for metastatic malignancies to the thorax, estimating the probability of malignancy in a lung nodule as a function of antecedent cancer history, analysis that the T descriptor in lung cancer should be adjusted to 2 cm (published in 2005), showing the outcome of wedge resection in very elderly patients compete with outcomes from lobectomy in lung cancer, and showing the impact of video-assisted thoracic surgery in lowering anticipated operative mortality in high risk groups. Most recently, I have participated in surgical task forces to establish Practice Guidelines. This work includes position statements regarding surgical management of elderly cancer patients with the international SIOG surgical task force and an analysis of prophylaxis against atrial fibrillation following general thoracic surgery with the STS surgical task force. I am currently heading an international task force to produce practice guidelines for the workup of lung nodules in elderly patients, balancing the regional probability of malignancy with geriatric assessments of the host ability to withstand therapy.
For 4 years I was the Director of the Cardiothoracic Resident teaching conference, creating a new curriculum following recommendations of the American Board of Thoracic Surgery. I have served as the official mentor to the first and second year residents in general surgery rotating on the Thoracic Surgery Service since the inception of this mentoring program 5 years ago. I have written the curriculum and serve as mentor for the MSIII rotation on the Thoracic Surgery Service for HMS students. Likewise, I have written the curriculum and serve as mentor for the MSIV rotating students from other medical schools on the Thoracic Surgery Service. I was an instructor in the Introduction to Clinical Medicine clerkship, teaching medical students the skills for obtaining histories and physical exams. I have served as faculty for professional courses in the US and Europe. I frequently provide didactic lectures to medical students and physician assistant students on topics in thoracic surgery. This work led to my appointment to the Education Committee of the Department of Surgery at BWH and to Chair of the Surgical Education Committee of the Massachusetts Chapter of the American College of Surgeons. I have also participated in both the European School of Oncology and Surgical Task Force of the International Society of Geriatric Oncology (SIOG). I was honored to receive the 2008 F. G. Pearson teaching award, voted on by the BWH Cardiothoracic Residents for the outstanding teacher of the year.
Most recently, I have established the Jack Mitchell Fellowship in Thoracic Oncology through the private contributions of Jack Mitchell, a grateful patient. Funds provide salary support and travel expenses for a general surgery resident to perform clinical research for a year, allowing me to provide individual mentorship to a single resident. Dr. Sarah Billmeier has been the first recipient of this fellowship.