Of the 7 billion people in the world, Thomson Reuters, chose only 3,200 for its recent list of “The World’s Most Influential Scientific Minds.” Vittorio Cristini, PhD, of the University of New Mexico Cancer Center, places among them. Dr. Cristini says, “I never expected this. It is truly amazing. I’m thrilled.”
The media company’s Institute for Scientific Information set out to find the best and brightest scientific minds for their 2014 list of “Highly-Cited Researchers.” They used citations as a measure of influence. “Citations offer a direct testament to work that scientists themselves judge to be the most important to ongoing research. By analyzing these citation connections, one can identify the most impactful people, publications, programs, and more,” says Gordon Macomber. Mr. Macomber is managing director of Thomson Reuters Scientific and Scholarly Research.
The 2014 list represents an elite group of scientists worldwide who published enough papers ranking in the top one percent of citations in any of 21 fields. The fields include mathematics, social science, and immunology. Thomson Reuters used a citation formula to analyze works published from 2002 through 2013. For Mathematics, the list contains a total of 99 scientists, including Dr. Cristini. Thomson Reuters last published its list in 2001.
In the last twelve months, Dr. Cristini published three papers that describe his fresh approach to studying cancer. In them, he introduced the “master equations of cancer.” He derived the equations from the insight that cancer drugs and cancer tissue, like everything else, must obey the laws of physics.
The master equations show how differently blood flows, lymph drains and molecules diffuse in cancer tissue. Dr. Cristini says, “one of the first results of this investigation demonstrated how profoundly different transport is in the tumor region within, say, the pancreas with respect to the normal pancreas surrounding it. Transport impairment is really a signature of cancer.”
Using results from routine clinical tests, Dr. Cristini showed that the equations could correctly predict how well that person would respond to treatment. The equations even predicted patient survival curves, the graphs cancer scientists use to describe the survival expectation of a group of individuals. Dr. Cristini’s current research uses the master equations to improve cancer treatment. “We want to use these mathematics to improve chemotherapeutic efficacy,” says Dr. Cristini.
In one set of projects, Dr. Cristini is working with Ursa Brown-Glaberman, MD, and Yehuda Patt, MD, at the UNM Cancer Center. They are developing clinical trials that will assess how changing the dose and timing of some drugs makes chemotherapy treatment work better for people. For example, the equations have shown that some people respond better to chemotherapy when treated with drugs like Avastin® in advance. Avastin® and other anti-angiogenic drugs prune blood vessels, especially the leaky blood vessels that tumors foster. This pruning helps the remaining vessels to better deliver blood and chemotherapy drugs to cells. Dr. Cristini explains, “You can actually improve blood flow, increase blood flow, because you eliminate all the inefficiencies.”
In a second set of projects, Dr. Cristini is working with C. Jeffrey Brinker, PhD, to design tiny particles that target cancer cells in the body. They are using the protocell that Dr. Brinker and his team developed as a starting point. Each protocell has a round silica core that carries the chemotherapy drugs. A lipid bilayer that mimics a cell membrane covers it and keeps the toxic contents inside until the right moment. Unlike chemotherapy, protocells can kill cancer cells and leave the healthy cells around them intact. But they need to get to the cancer cells first.
Using the equations for guidance, Dr. Cristini and Dr. Brinker are adjusting the physical features of protocells. These features affect how well they can move through cell layers to find cancer cells to kill. Dr. Cristini and Dr. Brinker can also adjust the proteins on the protocell surface to help them get through the cell layers. “We are going to use his [Dr. Brinker’s] experiments with nanoparticles in mice to prove the concept in vivo,” says Dr. Cristini. “We want to show that we can use nanoparticles to penetrate more effectively through the in vivo barriers.” But these methods help protocells find cancer cells only after they’ve left the bloodstream.
To steer through the bloodstream, Dr. Cristini and Dr. Brinker will work with Renata Pasqualini, PhD, also at the UNM Cancer Center. Dr. Pasqualini and her husband, Wadih Arap, MD, PhD, are experts on human blood vessels. They discovered that blood vessels display different proteins in different places of the body. Using these proteins as “zip codes,” they developed methods to guide drugs to specific places in the body. Dr. Pasqualini will place proteins on the surface of protocells so that they exit the bloodstream at the right place, near the tumor.
Using the protocells speeds the process of bringing this research to people battling cancer. “I don’t want to prove the concept with nanoparticles that will never be in a human body,” says Dr. Cristini. “The nanoparticles [developed by Dr. Brinker’s team] are compatible with humans. This really opens the door to revolutionizing treatment because these particles will be usable in people.”
Vittorio Cristini, PhD, is a University of New Mexico Professor of Pathology at the UNM School of Medicine and a UNM Professor of Chemical Engineering and of Biomedical Engineering. He is the Victor and Ruby Hansen Surface Professor in Molecular Modeling of Cancers and a ISI Highly-Cited Researcher - Mathematics. A Nuclear Engineer trained in Italy, Dr. Cristini also trained at Yale and the University of Minnesota in Applied Mathematics, Chemical Engineering and Materials Science. Dr. Cristini is a world-renowned expert in mathematical and computational biology, applied and computational mathematics, complex fluids and microfluidics, multidisciplinary materials science, and physical oncology. This expertise gives him a unique research perspective; he focuses on the development of predictive, multi-scale, patient-specific computational models of tumor growth and treatment response.
Ursa Brown-Glaberman, MD, is a University of New Mexico Assistant Professor in the Department of Internal Medicine, Division of Hematology/Oncology at the UNM School of Medicine.
Yehuda Patt, MD, is a University of New Mexico Professor in the Department of Internal Medicine, Division of Hematology/Oncology at the UNM School of Medicine. He is also Director of Gastrointestinal Oncology Research at the UNM Cancer Center.
C. Jeffrey Brinker, PhD, is a Fellow at Sandia National Laboratories and a University of New Mexico Distinguished and Regent’s Professor in the Department of Chemical & Nuclear Engineering.
Renata Pasqualini, PhD, is a University of New Mexico Professor in the Department of Internal Medicine, Division of Experimental Therapeutics and is also the Chief of the Division of Experimental Therapeutics at the UNM School of Medicine. Dr. Pasqualini also serves as the Associate Director for Translational Research and the Cancer Therapeutics Research Program co-Leader at the UNM Cancer Center. She is the Maralyn S. Budke Endowed Professor in Cancer Experimental Therapeutics.
Wadih Arap, MD, PhD, is a University of New Mexico Professor and Chief of the Division of Hematology/Oncology in the Department of Internal Medicine at the UNM School of Medicine. He serves as the Deputy Director of the UNM Cancer Center. Dr. Arap is the Victor and Ruby Hansen Surface Endowed Chair in Cancer Medicine.
The team that developed the protocell also included: Carlee Ashley, PhD (Sandia National Laboratories); Eric Carnes, PhD (UNM School of Engineering); David Peabody, PhD; and Cheryl Willman, MD. Dr. Brinker and Dr. Peabody are members of the UNM Cancer Center. Dr. Willman is the Director and CEO of the UNM Cancer Center.
“Mechanistic Patient-Specific Predictive Correlation of Tumor Drug Response with Microenvironment and Perfusion Measurements” is published in the August 12, 2013 online Early Edition of Proceedings of the National Academy of Sciences of the United States of America (http://www.pnas.org/). Authors include Elaine L. Bearer, Eugene J. Koay, Steven A. Curley, Vittorio Cristini.
“Mechanistic modeling identifies drug-uptake history as predictor of tumor drug resistance and nanocarrier-mediated response” is published in the November 4, 2013 online Edition of ACS Nano (http://pubs.acs.org/journal/ancac3). Authors include C. Jeffrey Brinker, Vittorio Cristini.
“Transport properties of pancreatic cancer describe gemcitabine delivery and response” is published in the March 10, 2014 Online Edition of the Journal of Clinical Investigation (www.jci.org/). Authors include Eugene J. Koay, Vittorio Cristini, Christopher H. Crane, Jason B. Fleming.
“Highly Cited Researchers 2014” represents some of world’s leading scientific minds. Over three thousand researchers earned the distinction by writing the greatest numbers of reports officially designated by Essential Science Indicators℠ as Highly Cited Papers—ranking among the top 1% most cited for their subject field and year of publication, earning them the mark of exceptional impact.
The list includes two other UNM faculty members, also within the Health Sciences Center: Xuexian O. Yang, PhD, Assistant Professor in the Department of Molecular Genetics and Microbiology; and, Mauricio Tohen, MD, DrPH, MBA, Professor and Chairperson of the Department of Psychiatry.
Learn more about the Thomson Reuters list at http://thomsonreuters.com/articles/2014/worlds-most-influential-scientific-minds-2014.
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