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Newest researchers challenge conventional ideas to make potentially transforming discoveries
Story by Charlotte Hsu; photos by Douglas Levere, BA ’89
SUPPLIES CROWD THE BLACK-TOPPED BENCHES in Anders Hakansson’s UB laboratory–test tubes, pipettes, centrifuges, bottles of chemicals, and glass jars holding clear and amber liquids.
At the end of one long table sits a stack of palm-sized plastic dishes coated with blood agar, a gelatinous substance in a brilliant red. In the ocean of clutter, these plates seem nondescript. But they are part of an experiment that could one day save lives in countries thousands of miles away.
“I’m not doing research
to be famous or anything. I’m doing it hopefully to make
an impact in people’s lives.”
Hakansson picks through the pile of agar-covered discs, examining half a dozen before finding one on which colonies of olive-green bacteria are still amassing. With time, these microbes, too, will die. HAMLET, a breast milk protein Hakansson is studying, has obliterated the Streptococcus pneumoniae growing on the other dishes. And, as Hakansson has discovered, HAMLET leaves no survivors.
Hakansson’s inquiries into HAMLET, Human Alpha-lactalbumin Made Lethal to Tumor Cells, began in the 1990s when he was pursuing a PhD in medical microbiology at Lund University in his native Sweden. While researching how breast milk protects against respiratory disease, he and his mentor, Catharina Svanborg, infected human cells with S. pneumoniae and exposed those cells to a milk fraction containing HAMLET.
Results were encouraging. The bacteria, responsible for pneumococcal infections killing more than 1 million people each year, died. And peering into a microscope, Hakansson noticed something else intriguing. In medical research, scientists often employ cancer cells as stand-ins for normal ones because cancer cells live longer but behave similarly in other ways. Hakansson and Svanborg were experimenting with lung carcinoma cells, and as Hakansson observed samples exposed to HAMLET, he saw that not only were the invasive bacteria gone; the cancer cells looked weaker, their nuclei shrunken and unhealthy.
“As the numbers of languages decline, we lose rich and distinct cultural variations from which we can learn a great deal in fields as far–ranging as anthropology, agriculture, linguistics, philosophy, geography and prehistory.” —Jeff Good
Hakansson and his mentor investigated. They learned that besides killing S. pneumoniae and Haemophilus influenzae—a culprit behind middle ear infections, bacterial meningitis and pneumonia—HAMLET destroyed tumor cells involved in breast, colon, kidney and prostate cancers, and gliomas, leukemias, lymphomas and sarcomas. For every kind of tumor tested, HAMLET initiated a “programmed cell death,” binding to cells’ outer membranes and triggering a chain of events that ended with fragmentation of the cells’ genetic material. The same fatal sequence wiped out colonies of S. pneumoniae and H. influenzae that met HAMLET.
Hakansson completed his doctorate in 1999. Afterward, he and Svanborg divided their work. Svanborg continued examining HAMLET’s tumor-fighting capabilities. Hakansson moved to the United States, where, as a University of Alabama at Birmingham postdoctoral fellow, he studied the protein’s effect on bacteria. In 2002, he set HAMLET aside to conduct research on cell biology at Harvard Medical School.
“By any measure, I
think my lab has
been so successful,
and I attribute this
to the continuity I
had and the support
that I had at every
step. It’s just been
such a very positive
Soon, however, he was ready to return to HAMLET. People worldwide were still dying of pneumococcal infections, and S. pneumoniae’s resistance to penicillin, the antibiotic doctors commonly prescribed to combat the organism, was growing. If he stayed at Harvard, Hakansson would have to juggle investigations of HAMLET with research on another scientist’s project. He had job offers from other institutions, including UB, which promised him his own laboratory.
“This was the best offer in terms of support,” says Hakansson, who joined UB in 2006. “I wanted to get going. I like the idea that what I do has a very direct impact, potentially, on diseases. It’s a motivation, that this could actually benefit people.”
HAKANSSON'S WORK is the stuff of tomorrow–science with the potential to advance our understanding of health and save lives. Some people may express surprise upon discovering that UB is home to this kind of innovation. But Hakansson is just one of many faculty members engaged in solving problems afflicting communities around the world. In today’s competitive market, UB is still attracting top talent, luring established researchers from places like Stanford University and inviting graduates of schools like the University of California at Berkeley to begin careers here. Fourteen hires since 2004 have received National Science Foundation (NSF) CAREER awards, the agency’s most prestigious prize for junior investigators.
“Everyone at UB is very productive and successful. It sounded like an atmosphere that I wanted to be part of.” —Jason Briner
Hakansson and fellow newcomers are making their mark in areas from medicine to the humanities. Gabriela Popescu, an assistant professor of biochemistry, is probing the human mind for clues to how we remember. Jeff Good, an assistant professor of linguistics, is documenting languages in danger of vanishing in Cameroon’s Lower Fungom Region. Jason Briner, an assistant professor of geology and director of UB ’s paleoclimate lab, has established himself as an expert in one of today’s hottest research areas: climate change.
Any scholar’s contributions are, by definition, small compared with the challenges that face the world today. Building proficiency in a field takes time, so each individual can become an expert only on a handful of topics. But the aggregate impact is impressive. Between 2005 and 2009, UB ’s research expenditures rose from $275.3 million to $349.4 million, a 27 percent increase. New faculty members are helping to drive that progress.
The National Science Foundation has supported Briner’s work with multiple six-figure grants, providing more than $1 million to study such topics as volcanism in the Arctic climate system, the Greenland ice sheet’s sensitivity to climate change and vanishing ice caps on Canada’s Baffin Island. Funding sources for Hakansson’s work on HAMLET include $443,000 from Buffalo’s John R. Oishei Foundation and $100,000 from the Bill & Melinda Gates Foundation, which awarded Hakansson a Grand Challenges Explorations grant. For his Cameroon project, Good has secured more than $340,000 from the NSF and the National Endowment for the Humanities’ Documenting Endangered Languages program. His inquiries have taken on heightened importance as forces, including urbanization and the trend toward monolingualism, catalyze a mass extinction of languages worldwide. Of the seven Good is studying in Lower Fungom–Abar, Fang, Koshin, Kung, Mbu’, Mundabli and Naki–the largest has, perhaps, a few thousand speakers.
“As the numbers of languages decline,” Good says, “we lose rich and distinct cultural variations from which we can learn a great deal in fields as far-ranging as anthropology, agriculture, linguistics, philosophy, geography and prehistory.”
Good came to UB in 2006 from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, where he had served as a senior research fellow after completing his PhD at Berkeley in 2003. Briner arrived in 2005 after completing postdoctoral training at the Institute of Arctic and Alpine Research at the University of Colorado at Boulder.
“I’m motivated, No. 1, by compassion. And I’m motivated to try to identify low-tech solutions with high impacts on public health.” —Pavani Ram
Popescu, a native of Romania, has a longer history with UB. She won a tenure–track position in 2006 but did her PhD and postdoctoral research here. She works with NMDA receptors, a brain protein that mediates communication between nerve cells and may play a role in disorders, including schizophrenia and Alzheimer’s disease. NMDA receptors are permeable to calcium ions and act like a spigot, controlling the flow of these ions into a neuron. High-calcium flows stimulate memory formation. Low flows lead to forgetting. Unchecked flows can cause cell death.
In 2004, Popescu appeared as lead author in a paper in Nature describing how stimulating NMDA receptors at a high frequency—about 100 times per second—can increase the strength of the connection between neurons, a quality scientists believe influences memory formation. The publication was a huge achievement. At the time, Popescu was a postdoctoral fellow working under UB biophysicist Anthony Auerbach, and in science research, Nature is a marquee journal—highly selective and widely cited.
Now, with nearly $2 million from the National Institute of Neurological Disorders and Stroke, Popescu is investigating mechanisms that control NMDA receptors—information that could spur development of drugs for neurological diseases. Grateful for her mentors’ guidance, she is giving back by training a new generation of researchers. One doctoral candidate in her laboratory graduated with four first–author publications and four job offers.
Briner is equally devoted to his students, taking part in an NSF-funded initiative that brings UB , Buffalo State College and Erie Community College together to develop programs to attract underrepresented minorities into the geosciences. He also takes undergraduates with him on research trips to the Arctic, teaching them how to use glacial and lacustrine records to interpret past impacts of climate change. Briner’s findings in recent years include the discovery, reported in Nature Geoscience in 2009, that glaciers like those that form the Greenland and Antarctic ice sheets can undergo periods of rapid shrinkage or retreat. That conclusion came from fieldwork demonstrating that a comparable prehistoric glacier in the Canadian Arctic receded in just a few hundred years, in a “geologic instant.” Similar events, if they happened today, would result in sharply rising global sea levels that would threaten coastal populations.
The influx of talent UB is enjoying is an early outcome of UB 2020, the long-range plan that envisions building the institution around “strategic strengths”—research groups that encourage scholars to collaborate across disciplines in eight broad areas. As of December 2009, UB had hired more than 100 faculty members into these clusters. Popescu and Hakansson are members of the strength in Molecular Recognition in Biological Systems and Bioinformatics. Good, the linguist, is in Cultures and Texts.
Every day, these minds are working on problems whose solutions are sometimes simple, sometimes high-tech. Hakansson and Pavani Ram, an assistant professor of social and preventive medicine who joined UB in 2005, are both battling disease. But their methods vary.
Ram, a former Centers for Disease Control and Prevention epidemiologist, is examining the effect of hand washing in preventing transmission of illnesses. She focuses on high-poverty areas, with one World Bank–funded project measuring how promotion of hand washing with soap affects diarrhea morbidity and other child development measures in Peru, Senegal, Tanzania and Vietnam. Bars of soap outfitted with motion sensors enable Ram and fellow investigators to pinpoint when research subjects clean their hands–an advancement over traditional data-collection methods that rely on observation.
“I’m motivated to try to identify low–tech solutions with high impacts on public health,” says Ram, a member of UB ’s Extreme Events: Mitigation and Response strategic strength. “I have in my office this sign that says, ‘27,000 children around the world died yesterday. What are you doing about it?’”
WHEN HAKANSSON explains what drives him to do science, his words reflect the motivations of many colleagues: “I’m not doing research to be famous or anything. I’m doing it hopefully to make an impact in people’s lives.
“I have no idea how this will pan out,” he says of his HAMLET studies. “But curiosity and the potential make it exciting. This job essentially means that I really don’t know what kind of experiments we will do next month. I love the environment of doing research—the interaction with students and the other people working in the lab. You have this team, and you’re working for the same goal.”
Here’s what Hakansson knows about HAMLET: The protein can kill a bacterium only if calcium is flowing into the cell, potassium is flowing out of the cell and protease activity is taking place within the cell. HAMLET appears to bind to a molecule called phosphocholine, found on the cell walls of S. pneumoniae and H. influenzae. And, perhaps most exhilaratingly, in the laboratory, bacteria do not show resistance to HAMLET, even under optimal conditions for resistance to develop.
Hakansson hopes such breakthroughs will convince the Gates Foundation to extend his funding with another $1 million. The American Lung Association has provided $80,000 to research whether HAMLET can be an effective treatment for pneumonia. But besides exploring HAMLET’s potential, Hakansson wants to continue studying how the protein works. Proteins are large molecules that break down quickly in the human body. Scientists could develop more stable drugs mimicking HAMLET if they knew more about the mechanisms it employs to kill bacteria. Similarities between how bacteria and tumor cells die following exposure to HAMLET mean Hakansson’s research could have implications for treating cancer.
Years have passed since Hakansson first encountered HAMLET. Even so, the work has just begun.
Charlotte Hsu, formerly a reporter for The Las Vegas Sun, is a staff writer with University Communications.
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