Up to 30 percent of HIV patients who are appropriately treated with antiretroviral therapies develop the chronic lung disease emphysema in their lifetime. Now, new research from Weill Cornell Medicine investigators has uncovered a mechanism that might explain why this lung damage occurs.

In the study, published May 9 in Cell Reports, investigators show how the human immunodeficiency virus, or HIV, binds to stem cells, called basal cells, which transform into other types of cells that line the airways. This process reprograms the basal cells, causing them to release enzymes, known as proteases, which can destroy lung tissue and poke holes in walls of the air sacs, where oxygen is exchanged.

“This research is important because although antiretroviral agents have turned HIV into a chronic, rather than deadly, disease, the viral reservoirs that remain in the lungs and other tissue continue to cause serious side effects,” said senior author Dr. Ronald Crystal, chairman of the Department of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at Weill Cornell Medicine, and a pulmonologist at NewYork-Presbyterian/Weill Cornell Medical Center. “Now that we have more information about how the HIV virus might cause emphysema, we can learn more about this potential enzyme target and work towards developing a therapy to prevent this lung damage from happening.”

Since antiretroviral agents have been used to treat the 18.2 million people in the world who are HIV positive and have access to these drugs—1.2 million of them in the United States—lifespans have greatly extended. But as HIV positive people have lived longer, they’ve also been diagnosed with degenerative disorders of the brain, heart and lungs at a higher rate than the general population. Many scientists have investigated how long-term HIV treatment leads to these outcomes. Some posit that the antiretroviral drugs themselves might contribute to these issues, while others have investigated the role of inflammatory cells. This study doesn’t discount earlier theories, Dr. Crystal said, but rather reveals a new mechanism by which the virus attaches itself to and reprograms basal airway cells, that should be further investigated as a possible therapeutic target.

To conduct this research, investigators took normal human airway basal cells, collected from the lungs of healthy nonsmokers, and under observation, exposed them to HIV for a set period of time. Rather than entering and reproducing in the basal cells, the virus instead bonded to the basal cells’ surface and reprogrammed them to start producing an enzyme, or protease, which can break down proteins and destroy tissues, called metalloprotease-9. Because investigators know that emphysema, a disease of the air sacs, starts in the airways, this finding suggests that when basal cells take on what Dr. Crystal called a “destructive phenotype,” they start eating away at healthy tissue, which in time, results in emphysema.

“To see how a virus modifies the function of a cell is an important observation,” Dr. Crystal said, noting that the Zika virus operates in a similar manner by infecting neural stem cells and changing their function, which leads to a birth defect characterized by a smaller than normal head and abnormal brain, called microcephaly.

“Our next step is to conduct additional research to determine what the preventative therapeutic target might be,” Dr. Crystal said, adding that the protease is a likely suspect, “and then, since basal cells are so important to normal lung anatomy and lung function, determine the other side effects of this re-programming.”

Dr. Augustine M.K. Choi, interim dean of Weill Cornell Medicine (first from left), and Larry Schlossman, managing director of BioPharma Alliances and Research Collaborations at Weill Cornell Medicine (second from left), join the third-round winners of the Daedalus Fund for Innovation. From third from left: Dr. Dolan Sondhi, accepting for Dr. Ronald Crystal; Dr. Stefan Worgall; Dr. Randi Silver; Dr. Edouard Mullarky, accepting for Dr. Lewis Cantley; Dr. Olivier Elemento; Dr. Haiying Zhang; and Dr. Gang Lin. The winners were honored at an event on Nov. 7 in The Starr Foundation-Maurice R. Greenberg Conference Center at the Belfer Research Building.

Seven winners have been selected for the third round of the Daedalus Fund for Innovation awards, an innovative Weill Cornell Medicine program that helps advance promising applied and translational research projects and emerging technologies that have commercial potential. The projects are wide ranging, designed to address patient needs in areas ranging from newborn medicine to cancer and infectious disease, brain injury and chronic illness.

The researchers — Drs. Lewis Cantley, Ronald Crystal, Olivier Elemento, Gang Lin, Randi Silver, Stefan Worgall and Haiyang Zhang — will each receive up to $100,000 for a period of one year to fund proof-of-concept studies that may help translate their early-stage discoveries into effective treatments for patients. The fund’s Scientific Advisory Committee, comprised of seasoned technology analysts from the biopharmaceutical and venture capital industries, selected the projects from 22 applications.

“The most challenging time for translational research is the period after initial discovery, in what is known as the ‘pre-competitive’ space, when investigators need to develop validation data in order to attract partners and investment from industry and/or the venture capital community,” said Larry Schlossman, managing director of BioPharma Alliances and Research Collaborations at Weill Cornell Medicine, who manages the Daedalus Fund. “The Daedalus initiative is designed to bridge the ‘development gap’ by providing philanthropic support at this critical juncture.”

• Dr. Lewis Cantley, the Meyer Director of the Sandra and Edward Meyer Cancer Center and a professor of cancer biology in medicine, is working to develop drug-like small molecules that block anabolic metabolism in triple negative breast cancer and non-small cell lung cancer — two aggressive malignancies with poor prognoses. Targeting serine synthesis could represent an effective treatment strategy for the cancers.
  
  
• Dr. Ronald Crystal, chairman of genetic medicine, the Bruce Webster Professor of Internal Medicine and a professor of medicine, is working on a gene therapy to prevent the neurodegenerative disease chronic traumatic encephalopathy, a condition that is strongly linked to repetitive brain trauma often caused by contact sports such as football. At the tissue level, brains affected by CTE accumulate a damaging form of the tau protein. Dr. Crystal is investigating a treatment approach in mice that uses a benign virus to deliver a therapeutic gene into the central nervous system. The gene would instruct neurons to secrete anti-phospho-tau antibodies, which would suppress the spread of toxic tau.
  
  

• Dr. Olivier Elemento, a Walter B. Wriston Research Scholar and associate professor of computational genomics in computational biomedicine and of physiology and biophysics, and his team have pioneered an experimentally validated artificial intelligence (AI)-guided approach called BANDIT (Bayesian ANalysis to determine Drug Interaction Targets). BANDIT uses big data to predict which protein targets small molecules will bind to in cells with 90 percent accuracy. This technology may dramatically speed up drug discovery, improve scientists’ ability to determine which diseases a drug would effectively treat, and identifies new ways to use existing drugs through the discovery of new unanticipated targets. Dr. Elemento hopes to expand BANDIT, which uses more than 20 million data points, so that he can identify new small molecules targeting relevant therapeutic targets in oncology, neurological and cardiovascular diseases, and expand the algorithms by integrating new data types into the AI engine.
  
  

• Dr. Gang Lin, an associate professor of research in microbiology and immunology, has been working with a class of drugs called proteasome inhibitors, which work to suppress the activity of the proteasome, a critical cell component that breaks down unneeded or damaged proteins and recycles their building blocks. Dr. Lin has developed proteasome inhibitors that target proteasomes in pathogens, but ignore those in humans, to treat bacterial and parasitic infections such as tuberculosis and malaria. He has also developed selective inhibitors for a special kind of proteasome in humans that interact with the immune system, called immunoproteasome, over the standard proteasome. These inhibitors have the potential to treat autoimmune and inflammatory disorders, and transplant rejection. Now, he’s seeking to derive fungal proteasome selective inhibitors to treat deadly fungal infections.
  
  
• Dr. Randi Silver, associate dean in the Weill Cornell Graduate School of Medical Sciences and a professor of physiology and biophysics, is studying how to alleviate chronic lung disease of prematurity, which is the most common preterm birth complication and may result, in part, from supplemental oxygen therapy. Dr. Silver will conduct safety and efficacy studies in mice using a chemical compound to see if it stabilizes a critical protein that becomes degraded during supplemental oxygen delivery. She hopes the data will lead to a new area of treatment for at-risk infants in the neonatal intensive care unit.
  
  
• Dr. Stefan Worgall, a distinguished professor of pediatric pulmonology and professor of pediatrics and of genetic medicine, is interested in devising a therapeutic strategy that addresses asthma’s underlying cause. Dr. Worgall demonstrated that diseased actions of an enzyme called SPT — which is responsible for synthesizing a key component of cell membranes called sphingolipids — is associated with airway hyperactivity that is a hallmark of asthma. Dr. Worgall plans to evaluate whether stimulating sphingolipid production or specific sphingolipids can be used to treat airway hyper-reactivity.
  
  
• Dr. Haiying Zhang, an assistant professor of cell and developmental biology in pediatrics, is focused on developing nanotechnology that incorporates information from membrane-bound “packages” secreted by cells to deliver drugs to specific tissues. The packages, called exosomes, carry proteins and nucleic acids such as RNA or DNA, and circulate through the body to distant tissues. Dr. Zhang and her team will test whether these exosome-nanoparticle hybrids can be used to target specific tissues and demonstrate nanoparticle drug delivery in animal tumor models. 

Weill Cornell Medicine and NewYork-Presbyterian Investigators Are Enrolling Subjects for a Phase I Clinical Trial to Establish Safety, Proper Dosing and Preliminary Efficacy

NEW YORK, NY (August 8, 2016) — A vaccine developed at Weill Cornell Medicine and NewYork-Presbyterian to blunt the effects of cocaine has advanced to clinical trials for testing in humans. After demonstrating that the vaccine prevented cocaine from reaching the brain in earlier animal studies, investigators are now enrolling active cocaine addicts in a Phase I randomized control study to test how it works in people.

"Cocaine addiction is a huge problem that affects more than 2 million people in the United States, and results in more than 500,000 annual visits to emergency rooms," said principal investigator Dr. Ronald Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medicine and a pulmonologist at NewYork-Presbyterian/Weill Cornell Medical Center. "While there are drugs like methadone designed to treat heroin, there aren't any therapeutics available to treat cocaine addiction. We hope that our vaccine will change that."

While most drugs that target addiction are designed to disrupt some process in the brain, this vaccine, called dAd5GNE, is meant to absorb cocaine in the bloodstream — well before it has had a chance to pass the blood-brain barrier and later produce a dopamine-induced high.

The dAd5GNE vaccine works by linking a cocaine-like molecule called GNE to a disrupted protein of an inactive adenovirus virus that typically causes cold-like symptoms, and is highly likely to produce an immune response. The immune system then unleashes antibodies that attack both the virus and the cocaine-like molecules connected to it. Once the body sees cocaine as the enemy, if the drug enters the bloodstream, the body will respond with a flood of anti-cocaine antibodies, each meant to gobble up cocaine like a Pac-man, Dr. Crystal said. This means that if someone who has received the vaccine uses cocaine, within seconds it passes from the lungs to the bloodstream, and once there, the antibodies attack.

"The goal of this vaccine is to prevent cocaine from reaching the brain," said Dr. Crystal, who is also the Bruce Webster Professor of Internal Medicine at Weill Cornell Medicine. "While we know that this works very well in animals, now we need to find out if the vaccine will cause enough anti-cocaine antibodies to be produced so that it works in humans, too."

Investigators are looking to enroll 30 subjects who are active cocaine users in the study, which is funded by the National Institute on Drug Abuse and the National Institutes of Health. The participants in this randomized, double-blind study will be divided into three consecutive, 10-person cohorts. Once the subjects have passed through an extensive screening process and are chosen, each cohort of 10 will be randomly split into seven receiving the vaccine and three receiving the placebo.

Before getting the vaccine, each participant will have to give up cocaine for at least 30 days, during which time they'll undergo frequent urine screens to test for cocaine use. Their first vaccine dose is administered as an injection in the shoulder. Additional boosters will be given every four weeks until the participant has received six total injections. After the final booster is given in week 20, subjects will undergo monitoring for another three months, until the study's conclusion after 32 weeks.

Each participant will have to meet with investigators two or three times per week to assess safety and efficacy. These meetings will include regular urine drug screens, EKGs, complete blood counts, and other measures of safety, as well as the review of any anti-cocaine antibodies in the participants' systems, self-reports on cocaine cravings and subjects' desire for other drugs and alcohol. Every subject will undergo standard drug dependency therapy throughout the study.

After the first group of 10 is finished, the second group will commence, followed by the third group. In total, 21 subjects will get the vaccine in escalating doses; nine subjects will get the placebo. The entire Phase I clinical study is expected to take about three years.

"Most people who become cocaine addicts want to give it up, but struggle to kick the habit in the long-term," Dr. Crystal said. "If this vaccine works, it could represent a lifetime therapeutic for addicts."

Participants will receive $25 per visit -- up to $2,400 for those who complete the study. To enroll in the study or for more information, please contact Aileen Orphilla at 646-962-2672 or email anticocaine@med.cornell.edu.

Weill Cornell Medicine

Weill Cornell Medicine is committed to excellence in patient care, scientific discovery and the education of future physicians in New York City and around the world. The doctors and scientists of Weill Cornell Medicine — faculty from Weill Cornell Medical College, Weill Cornell Graduate School of Medical Sciences, and Weill Cornell Physician Organization — are engaged in world-class clinical care and cutting-edge research that connect patients to the latest treatment innovations and prevention strategies. Located in the heart of the Upper East Side's scientific corridor, Weill Cornell Medicine's powerful network of collaborators extends to its parent university Cornell University; to Qatar, where Weill Cornell Medicine-Qatar offers a Cornell University medical degree; and to programs in Tanzania, Haiti, Brazil, Austria and Turkey. Weill Cornell Medicine faculty provide comprehensive patient care at NewYork- Presbyterian/Weill Cornell Medical Center, NewYork-Presbyterian/Lower Manhattan Hospital and NewYork-Presbyterian/Queens. Weill Cornell Medicine is also affiliated with Houston Methodist. For more information, visit weill.cornell.edu.

NewYork-Presbyterian

NewYork-Presbyterian is one of the nation's most comprehensive healthcare delivery networks, focused on providing innovative and compassionate care to patients in the New York metropolitan area and throughout the globe. In collaboration with two renowned medical school partners, Weill Cornell Medicine and Columbia University College of Physicians & Surgeons, NewYork-Presbyterian is consistently recognized as a leader in medical education, groundbreaking research and clinical innovation.

NewYork-Presbyterian has four major divisions: NewYork-Presbyterian Hospital is ranked #1 in the New York metropolitan area by U.S. News and World Report and repeatedly named to the magazine's Honor Roll of best hospitals in the nation; NewYork-Presbyterian Regional Hospital Network is comprised of leading hospitals in and around New York and delivers high-quality care to patients throughout the region; NewYork-Presbyterian Physician Services connects medical experts with patients in their communities; and NewYork-Presbyterian Community and Population Health features the hospital's ambulatory care network sites and operations, community care initiatives and healthcare quality programs, including NewYork Quality Care, established by NewYork-Presbyterian, Weill Cornell and Columbia.

NewYork-Presbyterian is one of the largest healthcare providers in the U.S. Each year, nearly 29,000 NewYork-Presbyterian professionals deliver exceptional care to more than 2 million patients.

For more information, visit www.nyp.org and find us on Facebook, Twitter and YouTube.

Quitting cigarettes may not improve smokers' lung function if they have already begun to develop chronic obstructive pulmonary disease, according to new research from Weill Cornell Medicine. The findings illustrate how cigarettes affect the lungs on a cellular level — which, the investigators hope, will help persuade smokers to stop as early as possible.

"The addiction to nicotine is very powerful," said senior author Dr. Ronald Crystal, chairman of the Department of Genetic Medicine, the Bruce Webster Professor of Internal Medicine and a professor of medicine at Weill Cornell Medicine. "But the earlier you can stop smoking before developing COPD, the better chance you will have at healthy lungs."

Endothelial cells, which form the lining of blood vessels, shed small bubble-like particles of plasma membrane called circulating endothelial microparticles, or EMPs. This process becomes accelerated when programmed cell death — called apoptosis — occurs; researchers can identify apoptotic EMPs by looking for specific antibody markers in the blood.

Weill Cornell Medicine investigators previously found that smokers have elevated levels of apoptotic EMPs coming from pulmonary capillaries compared to nonsmokers. To determine what happens to a smoker's apoptotic EMP levels after they cease smoking, researchers in the new study, published July 26 in Thorax, assessed the total and apoptotic EMP levels of a group of 138 nonsmokers, healthy smokers and COPD smokers. After baseline EMP levels were recorded, 17 healthy smokers and 18 COPD smokers successfully quit smoking. All subjects' EMP levels were then collected after three, six and 12 months.

Researchers found that both healthy and COPD smokers had elevated levels of apoptotic EMPs compared to nonsmokers, but only healthy smokers were positively impacted by smoking cessation. "When healthy smokers stopped smoking, their levels of apoptotic EMPs dropped back down to normal levels. But for COPD smokers, their EMP levels did not," Dr. Crystal said.

COPD, which causes partially irreversible airflow obstruction, is the third most common cause of death in the United States. Once a person develops the disease, lung function declines at an accelerated rate. "Studying the mechanisms by which COPD occurs, particularly very early on, is important so that we can target drugs that may be effective in terms of stopping the progression of the disease," said Dr. Crystal, who is also a pulmonologist at NewYork-Presbyterian/Weill Cornell Medical Center.

The Global Initiative for Chronic Lung Disease has set the standard for diagnosing COPD and determining its progression. Out of GOLD's four classifying stages of COPD, which range in intensifying severity from GOLD I to IV, most COPD participants were at GOLD I and II. "We purposely looked at people with the mildest form of the disease because it gives better insight into the mechanism," Dr. Crystal said. "When the disease is more severe, there are many pathological mechanisms, so it's harder to sort out what's going on."

Dr. Crystal added that this research is also important when it comes to developing COPD biomarkers, which are substances in the blood that provide doctors with insight into how certain organs, such as the lungs, are doing.

Qatar now has its own population-specific genome resource after researchers at Weill Cornell Medicine in New York and Qatar mapped the genomes of more than 1,000 Qatari nationals. This resource gives scientists a powerful reference tool that will facilitate efforts to identify genetic variations that cause serious and distressing conditions such as cystic fibrosis, sickle cell anemia and muscular dystrophy among the local population.

"This study is the first step in the development of precision medicine in Qatar," said co-senior author Dr. Ronald Crystal, chairman of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at Weill Cornell Medicine in New York. "Our genes decide how we respond to our environment and our risk for disease, and the variations in our genes are different for each population. With this initial description of the Qatari genome as a basis, and with future refinements to be made by the Qatari Genome Project, we now have the basis for defining the genetic risk of the Qatari population for disease, and how Qataris will respond to medical therapies."The new resource, published June 30 in Human Genome Variation, will also help doctors treating Qatari nationals to more effectively practice precision medicine, which involves analyzing a patient's genome in order to more effectively predict, diagnose and treat disease. A better understanding of the subtle variations in Qatari genomes will help researchers discover how certain ancestral genetic traits interact with environmental factors such as poor diet, lack of exercise and smoking to cause disease.

The project's completion is an important milestone in a new phase of genetic research, which has progressed from mapping the entire human genome — first achieved in 2003 after 13 years of investigation — to focusing on specific populations to identify correlations between shared heritage and susceptibility to particular diseases. This project is considered the most significant resource of genetic variants in any Arab population to date.

For the study, the research team — which comprised scientists from Weill Cornell Medicine-Qatar (WCM-Q), Weill Cornell Medicine, Sidra Medical and Research Center, Hamad Medical Corporation and Cornell University — gathered de-identified samples from more than 1,000 Qatari nationals who received care at Hamad Medical Corporation clinics. The scientists then used the advanced computing technology in the lab of the WCM-Q Genomics Core to analyze and map the genomes of each patient.

The scientists had previously identified three broad genomic groups within the Qatari population. The first group encompasses Bedouins, the second is a Persian or South Asian mixture, and the third comprises Qataris with sub-Saharan African heritage. In the latest study, supported by Qatar Foundation and Qatar National Research Fund, scientists achieved a higher resolution of ancestry. For example, individuals of Persian ancestry can now be distinguished from individuals of South Asian ancestry. This genetic diversity is important to recognize and understand as each group is likely to be susceptible to different conditions and react to environmental hazards in different ways, the investigators said.

Until now, researchers have usually attempted to identify disease-causing genetic variations by using powerful computers to compare the genomes of affected people with a global genome resource and searching for telltale differences between the two. Unfortunately, comparing the genomes of Qatari nationals with the global genome is problematic because the computer identifies tiny variations that may appear rare relative to the global genome average but are in fact very common among individuals of similar ancestries to the affected patient.

"One of the reasons genetics is complicated is that, in the genomes of every population we look at, we find millions of mutations, yet most of these do not actually cause disease - they appear to be harmless," said lead author Dr. Khalid Fakhro, an investigator at Sidra Medical and Research Center and an assistant professor in the Department of Genetic Medicine at WCM-Q. "So when a person with disease shows up in the clinic, it is more difficult than people imagine to identify the few potentially harmful mutations in a sea of mostly harmless variation."

The new population-specific resource mitigates this problem for Qatari nationals by providing a Qatari-specific genome resource, compiled from more than 1,000 Qataris whose families have enjoyed good health for at least three generations.

"Because many of the same harmless mutations are shared by members of the same population, using a population-specific resource makes it easier to identify abnormal mutations in the genome that do cause disease," Dr. Fakhro said. "Specifically, if we find a mutation shared by patients but it has never been observed in more than 1,000 ethnically-matched controls, we have higher confidence in its possible pathogenicity."

Given the shared heritage of Qatar's population with people in other parts of the Middle East and North Africa, the new Qatar Genome reference could also benefit patients across the region.

"This research has proven to be extremely exciting and worthwhile, not only for the new discoveries we have made but because there is great potential for clinical applications that will benefit patients in Qatar and the wider region," Dr. Crystal said. "We are very grateful for the support provided by Qatar National Research Fund and Qatar Foundation, without which this research could not have been undertaken."

A new gene therapy developed by scientists at Weill Cornell Medicine could eventually prevent the life-threatening effects of peanut allergy with just a single dose, according to a new pre-clinical study.

Peanuts are the most common food that induces fatal or near-fatal reactions in those who are allergic to them, yet preventive treatment is limited. In their study, published June 29 in the Journal of Allergy and Clinical Immunology, Weill Cornell Medicine investigators demonstrate in mice that one dose of a gene therapy boosts the efficacy of a drug that has been proven effective against peanut allergy but in its original form wears off in a matter of weeks.

"It appears that we've developed a drug that, with a single administration, might one day cure peanut allergy," said Dr. Ronald Crystal, chairman of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at Weill Cornell Medicine. "If we prove that it is safe and that it works in humans, it could change the way we treat allergic people."

Peanut allergies occur when a person's immune system overreacts to the allergen by producing an antibody called Immunoglobulin E (IgE), which stimulates the release of inflammatory chemicals. The most serious allergic reaction is anaphylaxis, which can cause severe respiratory effects that can be fatal.

The drug omalizumab, which is a type of protein called a monoclonal antibody that binds to IgE and neutralizes it, has been shown to protect against peanut allergy. Unfortunately, it has significant limitations, Dr. Crystal said. The drug must be injected and is only effective for two to four weeks, he said. "And it is expensive. It's not a practical preventative treatment for peanut allergy, even though it works."

In their study, Dr. Crystal and colleagues describe a new version of the drug that is effective in peanut-allergic mice with just a single dose. They took the genetic sequence from the monoclonal antibody in omalizumab and placed it in a virus, which they then injected into allergic mice.

"We essentially use the virus as a Trojan horse," Dr. Crystal said, "to transfer the monoclonal antibody into the mouse."

The researchers found that one dose of the gene therapy effectively prevented allergic reaction both in mice that were allergic but had never had a reaction, as well as in mice that had already been exposed to peanuts and had anaphylactic reactions.

"This scenario mirrors that of an allergic person who is accidentally exposed to peanuts," Dr. Crystal said. "If the therapy works as well in humans as in rodents, a single therapy may provide protection against allergic reactions for a lifetime."

The technique could also be effective against other IgE-mediated allergies, such as bee sting and shellfish, he added.

All of the work in this study was supported by Department of Genetic Medicine internal funds. Subsequent to the completion of this work, Weill Cornell licensed a patent disclosure relating to this work to Adverum Biotechnologies, a biotechnology company.  Dr. Crystal holds equity in Adverum as well as serves as a member of its scientific advisory board and a paid consultant to the company.  Drs. Crystal, Odelya Pagovich and Maria Chiuchiolo are inventors on the patent disclosure.

Smoking tobacco — even lightly — through water pipes significantly affects lung function and biology in young adults, a new study by Weill Cornell Medicine researchers shows.

A water pipe consists of a bowl that holds burning charcoal and tobacco. The smoke creates bubbles through water in the bottom of the pipe and is inhaled through a hose. Water pipes, also known as hookahs, have been used for smoking fruit-flavored tobacco for centuries in the Middle East. More recently, however, water pipe smoking has become popular in the United States, with at least 20 percent of young adults reporting having smoked this way.

Many users believe water pipes to be a safe alternative to cigarettes. But in their study, published March 23 in the American Journal of Respiratory and Critical Care Medicine, investigators found that hookah smoking is, in many ways, more dangerous than cigarette smoking.

"The fact that the smoke bubbles through water has led to the perception that the toxins in the tobacco are filtered out," said Dr. Ronald Crystal, chairman of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at Weill Cornell Medicine. "But the fact is, water pipe users are inhaling smoke into their lungs just like cigarette smokers do.

"We found evidence of multiple lung abnormalities in water pipe smokers," he added. "It is clear that even casual water pipe use is not safe."

One water pipe bowl holds the same amount of tobacco as a pack of cigarettes. Smoking that in one session exposes smokers to at least twice the amount of nicotine, seven to 11 times the amount of carbon monoxide, 100 times more tar, and 17 times the amount of formaldehyde in a pack of cigarettes, the study found. Those toxins have a measurable physical effect on young smokers, said Dr. Crystal.

The study looked at so-called light-use water pipe smokers – those who smoked no more than three bowls a week — whose average age was 24. The researchers evaluated both their clinical symptoms, such as coughing and production of phlegm, as well as biologic signs of lung damage.

They found that water pipe users had increased cough and sputum compared to non-smokers of a similar age, as well as reduced lung capacity. In addition, the hookah smokers showed significant abnormalities in the cells lining the airways in their lungs, suggesting that their lungs are being damaged.

"These results are concerning," Dr. Crystal said. "They suggest that, as these young people continue to smoke water pipes, they will develop clinical lung function abnormalities that can result in serious lung diseases."

Water pipe use is currently unregulated in the United States. More research is needed to determine the exact effects of inhaling water pipe smoke on long-term health, Dr. Crystal said.

"We need large-scale, epidemiologic studies, akin to the ones focused on cigarette smoking in the '70s and '80s," he said. "But for now, if I was advising a young person whether he should smoke a water pipe, I would say no."

Indigenous Arabs are direct descendants of humans who migrated out of Africa, before others continued on to colonize Europe and Asia, according to new research from Weill Cornell Medicine in New York and Qatar. In addition to shedding light on humanity's evolution, the conclusion highlights the importance of taking population genetics into account when researching disease and developing treatments.

The investigation, published online Jan. 4 and in the February issue of Genome Research, sequenced the genomes of 104 Arabian Peninsula natives and compared them with 1,092 genomes from worldwide populations. The researchers compared each pair of genomes in the sample, which allowed them to cluster research participants by genome similarity so that an evolutionary tree emerged. The genomes of indigenous Arabs resulted in a unique cluster separate from the initial African population, illustrating the formation of a distinct population. European and Asian clusters diverged after the Arab population.

These genetic groupings help disentangle the ancient path of human evolution. Scientists previously hypothesized that when humans migrated out of Africa 125,000 — 60,000 years ago, they passed through the Arabian Peninsula, colonized Europe and Asia, and later returned. By contrast, the present findings demonstrate that humans established the indigenous Arab population first.

"The indigenous Arab population was relatively isolated and yet they flourished and developed, as did Europeans, as did Asians. It's fascinating that all of these populations arose separately, yet became equally sophisticated and impressively advanced," said lead author Dr. Jason Mezey, an associate professor of genetic medicine at Weill Cornell Medicine and biological statistics/computational biology at Cornell University.

Additionally, identifying these distinct populations highlights how different groups can have subtle genetic differences — differences that demonstrate the importance of medical research being conducted based on specific populaces. Diabetes, for example, affects about 22 percent of the Qatari population. The scientists say that basing diabetes research and treatment development on Qataris' precise genetic makeup — rather than on another population — will ensure the most optimal health results.

"When you're researching genetics to try to understand influences on human disease, you have to compare apples to apples, not oranges to apples," said senior author Dr. Ronald Crystal, chairman of the Department of Genetic Medicine, the Bruce Webster Professor of Internal Medicine, and a professor of genetic medicine and of medicine at Weill Cornell Medicine. "This is important for understanding the risk of disease in the Arab population — or any population — and using the correct population for the basis of comparison."

Tremendous advancements in genetic technology enabled the scientists to arrive at their findings, they said. Previous genome sequencing methods only allowed researchers to primarily investigate mitochondrial DNA, a limited portion of a cell's DNA inherited from one's mother, and the Y — chromosome, another small piece passed from father to son. These two components only comprise a tiny fraction of the entire 3 billion base — pair genome. However, next — generation sequencing now provides investigators with the opportunity to sequence a person's complete genome, compare it with others, and shed light on complex patterns of human evolution.

"Everyone wants to know where they're from," said lead author Dr. Juan Rodriguez-Flores, an instructor in genetic medicine at Weill Cornell Medicine. "Genetics is one way of learning about your ancestors. We have a technology that allows you to go back farther than anyone previously has."

A non-invasive and quick lung function test frequently used to evaluate whether or not a smoker is at risk for developing pulmonary disease is likely mislabeling a significant percentage of smokers as healthy, a research team led by Weill Cornell Medicine investigators suggests.

A more specialized but still non-invasive test can more accurately represent this risk, the researchers found in a new study, published Nov. 5 in the European Respiratory Journal. If used more widely, doctors will be able to better predict who will develop chronic obstructive pulmonary disease, which is a condition defined by obstruction to expiratory airflows that makes breathing difficult. COPD, which includes smoking-induced emphysema, chronic bronchitis and non-reversible asthma, is the third-leading cause of death in the United States and affects more than 20 million people nationwide. While it is a condition caused by smoking, only 20 percent of smokers develop it. Based on this information, investigators sought to determine a way to better predict who might be affected.

"We wanted to figure out an accurate way to detect who is most at risk so that doctors can intervene earlier," said Dr. Ronald Crystal, chairman of the Department of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at Weill Cornell Medicine. "We found that a more comprehensive test works better, and using it will ensure that doctors aren't giving smokers a false sense of confidence that their lung function is normal."

The conventional lung function test, called spirometry, is widely available and can be performed in about one minute at a general practitioner's office. To take it, patients are instructed to inhale deeply and then blow out as hard as they can into a tube-like instrument. If less than 70 percent of air is blown out in that first second, and this ratio cannot be corrected by drugs that open up the airways, called bronchodilators, then the patient has COPD.

Dr. Ronald Crystal

"The problem with the spirometry test is that it doesn't give you the whole picture of lung function," Dr. Crystal said. Which is where the second, more comprehensive capacity diffusing test, which measures the function of a patient's air sacks, comes into play.

"If you think of the lung like an upside down tree, the trachea, or windpipe, is the trunk, the branches are the airways and the leaves are the air sacks," Dr. Crystal explained. "With smoking, those air sacks can be destroyed, and the diffusing capacity test measures their function."

Although it is similarly non-invasive, the diffusing capacity test is less portable, more expensive, and more difficult to run. For this reason, it is typically only used by pulmonologists.

To find out whether low-diffusing capacity levels correlated with an increased risk for developing COPD, investigators compared two groups of smokers — one with normal diffusing capacity levels and one with low diffusing capacity levels — all pulled from a larger pool of 1,570 New York City-based smokers with normal spirometry measures. Once divided into these groups, researchers randomly selected 59 people with normal diffusing capacity and 46 people with low diffusing capacity and followed them for about four years. Throughout this time, investigators ran sporadic lung function tests. All participants continued to smoke throughout the study, and most were about 50 years old, the typical age at which symptoms of lung disease appear.

While the vast majority of participants — 97 percent — with both normal spirometry tests and normal diffusing capacity stayed COPD-free over the four-year term, the researchers found that nearly one-quarter, or 22 percent, of people with the low diffusing capacity developed COPD during the study.

"This shows that smokers with normal spirometry results but low diffusing capacity are at significant risk for developing this serious and fatal disease," Dr. Crystal said.

It also means that many people who have normal spirometry results but never see a specialist or receive the diffusing test are being falsely told not to worry and that they're okay, Dr. Crystal continued. "Even with a normal spirometry test, patients and their doctors still have to worry that they may be at significant risk for developing COPD."

Dr. Lewis C. Cantley Awarded the Third Annual Ross Prize in Molecular Medicine

Dr. Lewis C. Cantley, the Meyer Director of the Sandra and Edward Meyer Cancer Center, has been awarded the third annual Ross Prize in Molecular Medicine from the Feinstein Institute for Medical Research and its open-access, peer-reviewed journal, Molecular Medicine.

Dr. Lewis C. Cantley. Photo Credit: John Abbott

The annual prize recognizes scientists who have made distinguished contributions to understanding how human disease develops and might be best treated, and who show promise for future contributions in the field of molecular medicine.

Dr. Cantley was recognized for his groundbreaking discovery of an enzyme called phosphoinositide 3-kinase (PI3K) and the signaling pathway that it controls. Dr. Cantley found that human cancers frequently occur due to activation of PI3K, a breakthrough that has led to the development of drugs that target that signaling pathway -- the first of which was approved by the U.S. Food and Drug Administration last year.

Dr. Cantley will receive the prize, which includes a $50,000 gift, during a ceremony on June 8 at the New York Academy of Sciences in Manhattan. Dr. Cantley, Dr. Harold Varmus, who recently joined Weill Cornell from the National Cancer Institute as the Lewis Thomas University Professor, and other prominent researchers will also give lectures during the event.

"It is a tremendous honor to receive this award," said Dr. Cantley, who is also the Margaret and Herman Sokol Professor in Oncology Research and a professor of cancer biology in medicine at Weill Cornell. "My laboratory discovered PI 3-kinase more than 25 years ago because of its co-purification with a variety of oncoproteins that caused cancers in mice and chickens. It was an unexpected discovery and it took us many years to understand why this enzyme, which produces a low abundant but powerful lipid, caused cancer. We now know that the lipid produced by PI 3-kinase is driving the growth of most human cancers."

Many PI 3-kinase inhibitors are now in clinical trials, and last summer, the first PI 3-kinase inhibitor was approved for treating chronic lymphocytic leukemia based on clinical trials conducted at the Meyer Cancer Center at Weill Cornell Medical College and NewYork-Presbyterian Hospital, Dr. Cantley said.

"It is likely that PI 3-kinase inhibitors will be useful in treating a wide variety of cancers as we learn how to best use these drugs in treating solid tumors," he added. "In accepting this award, I want to acknowledge an incredible group of brilliant students and postdoctoral fellows and collaborators who conducted the research that elucidated the PI 3-kinase pathway and its role in cancer."

Additional Awards and Honors

Dr. David Boyajian, an assistant professor of radiology, was recognized in October and December by NewYork-Presbyterian/Weill Cornell Medical Center with a Quality and Patient Safety Star Award (QPStar). The QPStar recognizes individual staff or teams across all disciplines that improve patient outcomes and prevent patient harm.

Dr. Ronald Crystal, chairman of the Department of Genetic Medicine, the Bruce Webster Professor of Internal Medicine and a professor of medicine and of genetic medicine, was invited to Drexel University College of Medicine as the Robert F. Johnston, MD Memorial Visiting Professor and gave the lecture, "Using the Genome as a Drug," on Oct. 22.

Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute, the Anne Parrish Titzell Professor of Neurology and a professor of neuroscience, gave the keynote address at the 2014 Brain Ischemia and Stroke Conference on Dec. 10 in Rome, Italy. The talk was titled "Innate Immunity and Neurovascular Homeostasis: From Stroke to Neurodegeneration." The conference was organized by the University of Rome and Mario Negri Institute to encourage the integration of basic and clinical research through exchanging ideas with scientists and clinicians across the world.