Undergraduate Research Papers Published By Neil

Dr. Caporaso has focused his research on understanding the molecular and population determinants of lung cancer and smoking. To that end, he and his colleagues designed the EAGLE (Environment And Genetics in Lung cancer Etiology) Study, a large, population-based case-control study of lung cancer in Italy, to provide a resource for descriptive, molecular, clinical outcome, and genetic/genomic studies. He incorporated novel behavioral aspects such as nicotine dependency, which has made possible a series of studies involving Time To First Cigarette (TTFC), in which he showed that short TTFC constituted a risk factor for lung cancer and later for COPD. Also, Dr. Caporaso and his colleagues have conducted a series of studies exploring biomarkers (microbiome, cytokines, metabolomics) in relation to smoking and lung cancer and plan to consolidate this work in risk model studies.

Dr. Caporaso’s second major research focus involves studying the etiology of chronic lymphocytic leukemia (CLL) in familial kindreds, and related hematologic and lymphoproliferative conditions including Hodgkin lymphoma, non-Hodgkin lymphoma, and Waldenström macroglobulinemia, among others. Dr. Caporaso, along with his colleagues and long-time collaborators, created an international consortium that identified monoclonal B-cell lymphocytosis (MBL) as a precursor condition to CLL. Within this group, he has been conducting follow-up studies of MBL as well as other investigations involving genetic analyses (GWAS and linkage), chromosome mosaic biomarker studies, single cell analyses, and planned studies of somatic mutations.

In addition, Dr. Caporaso has recently begun investigating the impact of circadian disruption on cancer.

Dr. Caporaso received his undergraduate degree in chemistry and cell biology research from Rutgers University, an M.S. in environmental science and his M.D. from the University of Medicine and Dentistry of New Jersey in 1980. After completing a residency in internal medicine in 1983, he joined the NCI as an oncology fellow in the Medicine Branch. He served as a research fellow and biotechnology fellow in the Environmental Epidemiology Branch of NCI. In 1996, he became Chief of the Pharmacogenetics Section, Genetic Epidemiology Branch (GEB). He served as Chief of GEB from 2011 through 2016.

Dr. Caporaso serves on the DCEG Biorepository Planning Group, the Research Evaluation Panel and Biomarker Advisory Committees of the American College of Radiology Imaging Network (ACRIN), the Steering Committee for the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Cohort Study, the Technology Planning Group for the Next Generation Cohort for DCEG, the Steering Committee of the International Lung Cancer Consortium, and the Cancer Genetic Markers of Susceptibility (CGEMS) Data Access Committee charged with implementing sharing of available NCI genome-wide association study data with the scientific community. Dr. Caporaso is the Genetic Epidemiology Editor of Cancer Biomarkers Epidemiology and Genetics and teaches at the George Washington Milken School of Public Health and the University of Maryland, as well as the Molecular Epidemiology Course in DCEG, and the Translational Research in Clinical Oncology (TRACO) course for oncology fellows at NIH.

October 01, 2015

Spotlight on Research: Neil Donahue - Particle Physics Comes Down to Earch

I do particle physics at CERN. When I say that to someone who regards herself as a particle physicist, I tend to get a puzzled look, because I am an atmospheric chemist. The particles I am interested in are actual objects consisting of molecules, not Higgs Bosons, and the physics (and chemistry) of interest is the processing that causes molecules to associate in the atmosphere to form clusters and then stabilize as new ultrafine particles.

At the CMU Center for Atmospheric Particle Studies, we study fine particles for two primary reasons: they kill a lot of people and they constitute one of the largest uncertainties in our understanding of climate change. Three of the top sources of mortality in the World Health Organization Global Burden of Disease report have to do with breathing fine particles: breathing polluted air, breathing over open cooking fires and breathing through a cigarette. Air pollution (or other pollution) is by no means a first-world problem, as health impacts fall disproportionately on residents of rapidly growing urban areas in the developing world (as anybody who visits Beijing or New Delhi can experience vividly).

The climate effects of fine particles arise because they influence the radiation budget, mostly incoming visible light (as opposed to CO2, which changes the way infrared radiation escapes from Earth). Particulate haze can scatter light back to space, and particles can change cloud properties by providing abundant nuclei for droplet formation. The uncertainty arises because to understand climate forces one needs to understand the difference between current (or future) conditions and pre-industrial conditions (typically taken to be 1750). We know how CO2 has changed since 1750 very accurately, and we understand the mass balance of CO2 as well — almost all of the increase is from fossil fuel use. We do not understand the change in fine particles — especially their number, which is what governs aerosol-cloud interactions. Particles come from two major sources: emission (mostly from combustion for small particles) and new-particle formation, or nucleation. It is almost certain that particle levels (both number and mass) have risen since the industrial revolution, but by how much is a tougher question.

Work in my own group has focused on the atmospheric chemistry of organic compounds. We have gotten a lot of recognition for this — in 2012 I was named a Fellow of the American Geophysical Union, and in 2014 I was recognized as a “highly cited researcher” by Thomson Reuters, along with only seven other faculty members at CMU (two of whom, Spyros Pandis and Ignacio Grossmann, are colleagues in Chemical Engineering). I became involved with a research consortium at CERN called CLOUD, http://home.web.cern.ch/about/experiments/cloud, which is dedicated to unraveling the chemistry and physics associated with new-particle formation in the atmosphere, and I now direct the CLOUD Virtual Institute, funded by the Science Across Virtual Institutes (SAVI) program of the National Science Foundation to support participation by CMU and Caltech in this largely European consortium.

CLOUD sits in the “shed” in the center of the CERN campus in Geneva, Switzerland, on the 1960’s Proton Synchrotron. The proton synchrotron now serves as the warm-up track to the Large Hadron Collider, as shown below. CLOUD, shown in the inset, is a large, 27 m3 stainless steel tank maintained at an astonishing purity; it may literally be the cleanest 27 m3 (at atmospheric pressure) on the planet. The protons in the proton synchrotron are in the hole, but they can also produce a beam of 3.6 GeV pions. The pions serve as an excellent and controllable mimic for cosmic rays, which are the main source of ions in the atmosphere. Ions are one of many things that can catalyze new-particle formation, and they also can “pre charge” molecular clusters so we can observe them with mass spectrometers. So, whenever the LHC is in operation, we can steal some “spills” from the proton synchrotron and do science in the shed.

I joined CLOUD when the consortium became interested in the role that organic compounds can play in the formation of new particles and their growth between 1 nm diameter and 3 nm diameter, where they are especially vulnerable to losses because of their high diffusivity. Gas-phase oxidation chemistry of organics by atmospheric oxidants such as ozone and the hydroxyl radical can produce a vast array of highly functionalized product molecules, rather like an undergraduate organic synthesis gone horribly wrong. Some of those products have such low vapor pressures (much less than 10-12 atmospheres) that they can nucleate directly, and others have slightly higher vapor pressures and can condense in succession as the particles grow a little bit. We have been studying the novel oxidation chemistry that can take C10 hydrocarbons and produce C10 oxygenated organics with up to 12 oxygen atoms on the carbon backbone in a single generation of chemistry. High-resolution mass spectra like the one on the previous page show us unambiguously that this chemistry occurs, but we are only beginning to understand the mechanisms. At the same time, we are developing the theoretical tools to let us describe the thermodynamics of these very complicated organic mixtures in particles that contain between just a few and a few hundred molecules. Some of that involves quantum chemistry, and some involves tried and true methods for vapor pressure estimation applied to this novel system. To date, we have published one paper in Nature (Almeida et al., 2013), one in Science (Riccobono et al., 2014) and two in PNAS (Schobesberger et al., 2013; Kürten et al., 2014). Four more are under review in Science and Nature. For the first time we have been able to reproduce new-particle formation in the laboratory that occurs at the formation and growth rates observed in the atmosphere and produces particles with the observed composition. We are gaining much more insight into the new-particle formation process before the industrial revolution, and the tools developed here at CMU are playing a central role in that growing understanding.

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