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Tag: grants

Researchers to test drug candidates to treat malaria

by Donna Huber

Belen Cassera
Belen Cassera is leading a research team that will test two new drugs for the treatment of malaria. The team’s work will be funded by a $3.7 million grant from the National Institutes of Health. (Photo credit: Amy Ware)

Though malaria was eliminated from the U.S. 70 years ago, the mosquito-borne disease caused by the Plasmodium parasite is still rampant in many parts of the world – nearly 40% of the world’s population is at risk of contracting it, and nearly 450,000 people die each year from it. With the rise of drug resistance, the current medical treatments aren’t enough to end this disease.

“Every drug treatment currently in use for malaria is showing resistance or reduced efficacy,” said Belen Cassera, a member of the University of Georgia’s Center for Tropical and Emerging Global Diseases. “Furthermore, there are very limited treatments for the most vulnerable – children and pregnant women. Over 60% of deaths are children under the age of 5.”

Cassera is co-leading the research team that recently received a $3.7 million grant from the National Institutes of Health to test two new drug candidates.

“These compounds are really promising as they are easy to synthesize, cheap, reliable, have a low toxicity profile, and kill the parasites fast,” said Cassera, associate professor in the Department of Biochemistry and Molecular Biology, part of the Franklin College of Arts and Sciences.

What’s unique about these compounds is that they can kill the parasite in three development stages in humans. Current treatments only target the blood stage, which is when clinical symptoms appear.

The life cycle of the Plasmodium parasite is complex. When an infected mosquito bites a person, just a small number of parasites – usually less than a hundred – are injected into the bite site and then travel to the liver, where they multiply in number to thousands. Once their numbers are sufficient enough, they invade the bloodstream and infect red blood cells.

When the number of parasites reaches 100 million, symptoms occur and some of the parasites develop into a sexual form, also known as the gametocyte stage. This is when symptoms occur. The sexual form is then transmitted back to the mosquito when the person is bitten again.

This complex life cycle makes it difficult to find a treatment that will eradicate the disease. Breaking the cycle of transmission between humans and mosquitos is key to accomplishing that goal. That’s why the team is excited about discovering compounds that can attack the parasite on multiple fronts.

“We are really a powerhouse team,” said Cassera. “We have a leading medicinal chemistry expert in Paul Carlier, the robust parasitology resources of UGA, and Max Totrov brings the machine-learning expertise to tie it all together.”

Cassera is a UGA Innovation Fellow, and she also credits the knowledge gained at UGA’s 2019 Innovation Bootcamp with helping her prepare a grant proposal that would be of particular interest to drug manufacturers.

Cassera has been working for several years to identify new drug candidates, along with Carlier, a professor in the Virginia Tech College of Science’s Department of Chemistry and director of the Virginia Tech Center for Drug Discovery, and Max Totrov, a computational chemist at Molsoft.

“We started working with the Malaria Box from Medicines for Malaria Venture, and the discoveries we made in basic malaria biochemistry and medicinal chemistry really springboarded us to a new level and led us in this new direction,” Cassera said.

Cassera is leading the testing of the new chemical variations of the antimalarial compounds prepared by Carlier for effectiveness in cellular and animal models.

“My lab will be looking at levels of toxicity, the potential for resistance, and how well they work both directly on the parasite and in infected mice,” she said. “We’ll be performing the studies for making the go/no-go decision for these compounds.”

A joint patent application for both drug candidates was recently filed, and the team is optimistic that their research will yield fast-acting candidates for advanced pre-clinical evaluation.


This story originally appeared at UGAResearch

UGA’s Rozario receives NIH Director’s New Innovator Award

By Alan Flurry

(Photo courtesy of Tania Rozario)

University of Georgia faculty member Tania Rozario has received a $2 million grant from the National Institutes of Health Director’s New Innovator Award Program, which supports early-career investigators of exceptional creativity who propose high-risk, high-reward research projects.

Rozario is an assistant professor with a joint appointment in the Franklin College of Arts and Sciences Department of Genetics and the Center for Tropical and Emerging Global Diseases.

Among the study of tropical diseases worldwide—and particularly among the parasites that cause disease—worms are a largely neglected disease agent, despite being a source of widespread problems that affect both health and economic output. Even within the study of worms, parasitic flatworms like tapeworms represent an understudied group. However, free-living flatworms like planarians are the focus of significant research because of the organism’s dynamic regenerative capacity, which presents intriguing parallels to their parasitic cousins.

Planarian flatworms cut in two will make two new worms, and cut into 10 pieces will result in 10 worms. They are the Ferrari of regenerators, according to Rozario.

“As part of its normal life cycle, a tapeworm sheds large parts of its body and then regrows this lost tissue,” Rozario said. “It has this natural regenerative-like ability, which is very promising from a basic biology standpoint, to understand how stem cells and regeneration functions in these worms.”

Taking advantage of both extensive past research and the much more sophisticated tools of today, Rozario envisions a melding of developmental biology with parasitology as a new approach to understand the parasite. She is using the rat tapeworm, Hymenolepis diminuta, to re-establish a model organism that had been a favorite model among parasitologists in the early-mid 20th century but was left behind by the molecular biology revolution.

Flatworms have incredible capacity for regeneration, according to Tania Rozario, who studies them as agents of parasitic disease. For example, this rat tapeworm is capable of growing thousands of segments and can regenerate segments following amputation.


“One of the major drivers is trying to understand the diversity of the stem cell milieu in these tapeworms,” Rozario said. “We’ll try to parse out the interaction between the diversity of stem cells present and the local signals that then allow the worms to regenerate and make thousands of segments. These interactions are likely crucial for development of both female and male reproductive structures, which exist in each segment of the animal.”

“Dr. Rozario brings a new and exciting area of research to UGA, and her enthusiasm for her research is phenomenal,” said Nancy Manley, Distinguished Research Professor and department head for genetics. “Her success in getting this prestigious award speaks to her talent and the quality of her science. We are enthusiastic to have her as our newest colleague.”

“I am excited that Dr. Rozario has joined us at UGA,” said Dennis Kyle, GRA Eminent Scholar in antiparasitic drug discovery and director of the Center for Tropical and Emerging Global Diseases. “Her pioneering work is ushering in a new era whereby tapeworms can serve as model organisms. The prestigious NIH Director’s Pioneer Award is evidence of the creative approach she is undertaking to better understand these interesting parasites.”

“It’s important that we study the monsters in our midst so that we can learn from organisms in our environment that have these really out-there, unique physiological capabilities,” Rozario said. “We can learn about how they have evolved strategies to thrive in their specific niche, but they can also teach us something more fundamental about biology that could be broadly applicable.”

microscopy of tapeworms
In these Hymenolepis diminuta tapeworm necks, dividing cells—including stem cells—are depicted through color-marking in the image. (Image courtesy of Tania Rozario)

NIH awards CTEGD $1.9 million to support training in tropical and emerging global diseases

UGA’s Center for Tropical and Emerging Global Diseases has been awarded $1.9 million from the National Institutes of Health to continue its pre- and post-doctoral training program for the next five years. First funded in 2004, CTEGD has received nearly $2 million from NIH to train the next generation of scientists in the fight against neglected tropical diseases. The new funding will support additional fellowships and new training initiatives.

Every year, parasitic diseases are responsible for more than a million deaths and leave hundreds of millions more with chronic infections lasting years. However, there are few U.S. programs that specifically train researchers in this field.

CTEGD is recognized as a pre-eminent research center that brings together the largest number of laboratories in the U.S. to study the full gamut of parasitic diseases, which are highly prevalent in sub-Saharan Africa, South America and Asia. Often, these diseases are the consequence and cause of poverty, and they are increasingly emerging (or re-emerging) in industrialized nations. Most of these diseases have no cure and few treatment options, and growing drug resistance complicates the fight against them. Now more than ever, researchers are needed in the field of parasitology and tropical diseases in order to improve global health.

NIH recognizes the need for researchers trained in parasitology and tropical disease, as well as UGA’s and CTEGD’s ability to fill it, by providing funding for two additional pre-doctoral fellowships. CTEGD will now be able to award five pre-doctoral fellowships and two post-doctoral fellowships each year

“This is incredibly exciting,” said Dr. Silvia Moreno, program director of CTEGD’s Training in Tropical and Emerging Global Diseases (TTEGD) and Distinguished Research Professor in cellular biology. “It’s a very competitive program and having additional pre-doc positions funded is even more exciting. Our program offers a great environment for training in parasitology which is the result of the hard work of the CTEGD community plus great UGA institutional support”.

The support of the university community

UGA’s support of the program has been instrumental to its continuing funding by NIH. The state-of-the-art equipment and facilities available to trainees allow them to learn cutting-edge techniques and technologies.

Under the direction of Vice President David Lee, the Office of Research has committed significant support over the next five years to fund the capstone experience, which allows each fellow to conduct research in an international setting, and two additional pre-doctoral assistantships.

“The Center for Tropical and Emerging Global Diseases is one of the key components of UGA’s strength in the wide-ranging fight against human disease,” Lee said. “The exceptional training that students and posdocs receive at CTEGD is a point of significant pride for the university, and I am committed to supporting the further growth of the Center and the TTEGD program.”

The Office of Postdoctoral Affairs will continue to partner with CTEGD to provide grant-writing workshops and career development opportunities for post-doctoral fellows. Last year, CTEGD organized a workshop on NIH’s K-Award grants that are available to post-doctoral fellows.

Franklin College of Arts & Sciences has also committed over the next 5 years to match funds from CTEGD to provide for a mini-sabbatical program a faculty member from a local college or university, along with up to two undergraduate students from that school, to spend a semester working in a CTEGD laboratory. The goal of this program is to increase awareness of post-undergraduate opportunities and spark interest in neglected tropical disease research.

Committed to training the next generation of scientists

To date, 37 pre- and post-doctoral fellows have received training support through the NIH T32 Training Grant. The fellowships awarded by CTEGD include a stipend, travel award, health insurance, and some financial support for research supplies. Pre-doctoral fellows also receive a tuition waiver. In the past 15 years, graduate students have assisted in field studies in Haiti, Tanzania, Argentina, Thailand, Ecuador, and Kenya as part of their capstone experience.

“My trip to Ecuador was unimaginably enriching,” said Dr. Manuel Fierro, a former T32 fellow who completed his Ph.D. this year. “I was presented with the way great research is done in a setting containing fewer resources than in the US and it gave me important connections for my professional development. More importantly, it gave me hope of returning to my home country and continue applying my parasitology training.”

Trainees have gone on to positions in academia, government and industry. They have secured positions as post-doctoral fellows, staff scientists, and assistant professors at such institutions as the Centers for Disease Control and Prevention, Food and Drug Administration, the National Institutes of Health, University of California, Emory University School of Medicine, Tufts University’s Cummings Veterinary Medical School, and Wellcome Centre for Anti-Infective Research in Scotland.

Embarking on its 16th year this fall, CTEGD is committed as ever to increasing rigor, diversity, and career development in its training program. New requirements for post-doctoral trainees, more rigorous training for new trainers, strategic recruitment initiatives to target underrepresented minorities, and expansion of training to include large data mining and computer science are just a few of the changes the program will undertake over the next five years.

“The T32 training grant represents the core of CTEGD’s effort to prepare the next generation of scientists to tackle the scourge of the neglected parasitic diseases of mankind,” said Dr. Dennis Kyle, director of CTEGD. “The renewal of this award allows us to expand our efforts and is recognition of the excellence of our students, postdocs, staff, and faculty.”

Researchers receive $2M NIH instrumentation grant

by Alan Flurry

The National Institutes of Health has awarded University of Georgia researchers $1.956 million for a high-resolution mass spectrometer that will enhance capabilities for scientists in many fields across campus.

The award by the NIH High End Instrumentation program, which provides grants in the range of $600,000 to $2 million for a variety of expensive instrumentation, including MRI imagers, electron microscopes, DNA sequencers, and mass spectrometers, was one of 30 awards made in the program, and one of only six mass spectrometer requests funded in the 2018 cycle.

The grant funded a 12 Tesla Bruker Solarix FTMS, a high-resolution mass spectrometer capable of measuring molecular weights with precision accuracy that can be applied to molecules ranging in size from small metabolic products to intact proteins and protein complexes. It can also provide molecular structure through a multidimensional analysis method known as tandem mass spectrometry. The instrument will be used to support research in metabolomics and glycomics, the analysis of genetic, physiologic and pathologic aspects of sugar molecules involved in all biological process from modulating cell function to determining cancer development.

“This instrument will enhance the research capabilities for a number of scientists in chemistry, the biological sciences and biomedical research, and will help foster interdisciplinary research projects between groups in a number of departments and colleges at the university,” said Jon Amster, professor and head of the department of chemistry and principal investigator on the grant.

Over a dozen researchers will be major users of this instrument, which will be housed in the Amster laboratory in the department of chemistry.

“The new 12T FT-ICR instrument will greatly improve our ability to perform metabolomics analysis, especially regarding to the identification of unknown metabolites, since this instrument has higher accuracy and resolving power than the current instruments at UGA,” said Belen Cassera, associate professor of biochemistry and molecular biology, member of the Center for Tropical and Emerging Global Diseases, and co-principal investigator on the grant. “This type of grant can be particularly difficult to obtain and it is a privilege for me to be part of an amazing team of investigators that put together this application.”

“Virtually every metabolomics project we have going right now will benefit from this new instrumentation grant,” said Art Edison, GRA Eminent Scholar, professor of biochemistry and molecular biology, and a co-principal investigator on the grant. “High resolution mass spectrometry is a very important tool for the analysis of complex biological mixtures and unknown metabolite identification in applications ranging from human disease to carbon cycling in the ocean to model organisms for pathway analysis.”

Of the 104 NIH shared instrumentation grants made this year during 2018, only 10 were in the range of $1.9 million to $2 million.

UGA Researcher Seeks to Unlock Secrets of Malaria Parasite

malaria parasites
Super-resolution microscopy showing malaria parasites infecting human red blood cells. Image credit: Muthugapatti Kandasamy, Biomedical Microscopy Core

Vasant Muralidharan and his research team at the University of Georgia’s Center for Tropical and Emerging Global Diseases are making great strides in understanding how the malaria parasite hijacks red blood cells to cause disease but many of the parasite’s strategies remain elusive.  A new $1.875 million grant from the National Institutes of Health will allow them to continue this research.

Malaria is a parasitic disease that infects nearly 220 million people and kills nearly half a million people every year. Almost all the deaths occur in young children and primarily in sub-Saharan Africa. The parasite Plasmodium falciparum invades human red blood cells which directly leads to malaria symptoms that include headaches, muscle pain, periodic fevers with shivering, severe anemia, trouble breathing, and kidney failure. The parasite can also cause the most severe forms of malaria, such as cerebral malaria which can lead to brain damage, coma and death, and placental malaria, which occurs in pregnancy and can be life-threatening to both the mother and fetus.

Complete control of the infected red blood cell is required for parasites to grow and spread. The malaria parasite remodels the host cell by exporting hundreds of parasite proteins across numerous membranes that transform all aspects of infected red blood cells to suit its needs. The export of these proteins by P. falciparum to the host red blood cells is a unique parasite-driven process that is associated with many of the clinical manifestations of malaria, including death. The mechanisms which these proteins are exported are unknown.

“Exported proteins, many of them absolutely essential for the growth of the parasite, are recognized and sorted throughout the trafficking process by dedicated machinery that we have only now begun to understand,” said Muralidharan, assistant professor in the department of cellular biology.

His lab hopes to reveal unique protein trafficking mechanisms of P. falciparum that may be targets for antimalarial drug development.

 “We expect that this project will significantly advance our understanding of the protein export pathway in P. falciparum and how key decisions are made within the parasite that usher exported proteins to their site of action in the infected red blood cells,” concluded Muralidharan.

National Institutes of Health Award R01 AI130139 “Elucidating the trafficking mechanisms of effector proteins to the Plasmodium infected red blood cell.”

Researcher receives $5.2 million to develop affordable diagnostic test for Chagas disease

Dylan Orr

Athens, Ga. – An international team of researchers led by infectious disease experts at the University of Georgia has received $5.2 million from the National Institutes of Health to develop a more accurate, affordable diagnostic test for Chagas disease, a parasitic infection that kills more than 50,000 people each year in Central and South America.

Caused by the parasite Trypanosoma cruzi and spread by blood-feeding insects commonly known as “kissing bugs,” Chagas disease is considered by many to be the most neglected of the neglected tropical diseases. While it is endemic to Latin America, Chagas disease is a growing threat in the U.S. and Europe.

Currently, there are only two drug treatments available; however, their usage is limited due to severe adverse reactions and the length of treatment required.

“Fortunately, there are a number of new drug discovery efforts in Chagas disease. But a major limitation is the difficulty in comparing the relative efficacy of current drugs to newly developed ones,” said Rick Tarleton, UGA Athletic Association Distinguished Research Professor of Biological Sciences in the department of cellular biology and Center for Tropical and Emerging Global Diseases. “One simply can’t wait for 10 years (as current protocols require) to determine if a new drug is better than the existing ones.”

In Chagas disease, the number of parasites in chronically infected individuals is extremely low, making detection of parasites an unreliable test to determine if an individual is infected. Instead, the researchers have focused on the body’s response to infection by measuring the unique antibodies that the immune system creates in response to exposure to T. cruzi.

Tarleton and his UGA colleagues have already developed a successful multiplex blood test that measures antibodies to multiple T. cruzi proteins. While their test has proven to be useful in the laboratory, it is also expensive.

The primary goal of their current project is to make the test more sensitive by expanding the number of T. cruzi antibodies it can detect. But the researchers are also developing techniques to make the test more affordable so that it can be used in diagnostic centers in endemic countries.

“By monitoring a broader range of immune responses, we can achieve a rapid and reliable detection of changes in these responses after treatment. And moving from the current bead-based assay to an array platform makes the reagents and the detector for reading the assay much more affordable,” said Tarleton.

The “gold standard” for determining a cure is for a patient to convert from seropositive to seronegative, meaning that a blood test does not detect any T. cruzi antibodies. The conventional blood test requires a minimum of 24 months to show a decline in antibody response, and complete conversion to a negative blood test can take up to 10 years.

Over the past 12 year, the Tarleton laboratory and CONICET research scientist Susana Laucella’s laboratory in Argentina have shown antibodies tested by the multiplex method are potential surrogate indicators of treatment success. They believe this method will detect significant decline in antibody levels in less than 12 months.

In an effort to more rapidly determine treatment success, the project will also investigate additional potential markers of patients being cured, including antibodies to carbohydrate epitopes and changes in numbers of plasmablasts, the cells that secrete antibodies.

“We are looking for the earliest signs of treatment efficacy,” said Tarleton. “As parasite numbers are reduced due to treatment, we expect, based on data from other systems, that one of the first detectable changes will be in the immune cells that are responding to the presence of parasites and producing antibodies, the plasmablasts.”

The researchers will also be exploring the phenomenon of spontaneous cure-a cure in the absence of treatment-as only anecdotal information is currently available.

“The immune response to T. cruzi infection is actually very strong and as a result, spontaneous cure occurs,” said Tarleton. “However the frequency of cure without treatment is not known, nor are methods available that discriminate between those with active, chronic infections and those who have cured.”

Approximately 20 percent of individuals receive mixed results from conventional blood tests for T. cruzi infection. This is a large number of potentially infected people to leave untreated. However, current therapies have such severe side effects doctors often do not prescribe. Additionally, understanding why some individuals can “cure themselves” could lead to new treatments for the disease.

“The key to the success of this project will be the bringing together of basic research findings with great technology and access to patient groups and their samples-some collected over decades. That is what the partners in this work collectively bring to the problem,” said Tarleton.

Tarleton is joined by collaborators at the Blood Systems Research Institute, the University of California, Irvine, Emory University as well as partners in Argentina and Brazil. Their project is supported by the National Institutes of Health under award number R01-AI125738.

UGA Center for Tropical and Emerging Global Diseases
The University of Georgia Center for Tropical and Emerging Global Diseases draws on a strong foundation of parasitology, immunology, cellular and molecular biology, biochemistry and genetics to develop medical and public health interventions for at-risk populations. Established in 1998, the center promotes international biomedical research and educational programs at UGA and throughout Georgia to address the parasitic and other tropical diseases that continue to threaten the health of people throughout the world. For more information, see

Writer: Donna Huber
Contact:Rick Tarleton

UGA receives $1.25 million for training of tropical, emerging global diseases researchers

trainee Charles Rosenberg

Athens, Ga. – The University of Georgia’s Center for Tropical and Emerging Global Diseases was awarded $1.25 million by the National Institutes of Health to continue training graduate and postdoctoral students over the next five years who can help address the growing threats of parasitic diseases.

Every year, diseases caused by protozoan and helminth parasites are responsible for more than a million deaths and cause hundreds of millions more cases of severe or subtle morbidity due to chronic infections lasting years.

“The University of Georgia is uniquely positioned as a training ground for the next generation of parasitology and tropical diseases researchers,” said Silvia Moreno, a professor of cellular biology in the Franklin College of Arts and Sciences and co-director of the center’s T32 trainee program.

The internationally recognized research center brings together the largest number of laboratories in the U.S. that collectively conduct research on the full gamut of parasite diseases. These diseases are highly prevalent in sub-Saharan Africa, South America and Asia. Often they are the consequence and cause of poverty. They also are increasingly emerging or re-emerging in the U.S. and other industrialized nations.

The CTEGD training program is currently in its 10th year. Past trainees have gone on to successful careers as staff scientists at the Centers for Disease Control and Prevention and as faculty, postdoctoral scholars or medical and veterinary scientists at leading universities and research institutes.

“The breadth and culture of our program instills trainees with the ability to not only translate basic scientific findings into tool development and the implementation of interventions, but also to identify and formulate fundamental research questions beyond the context of parasitic disease itself,” Moreno said.

“This program is very attractive to students,” said Boris Striepen, Distinguished Research Professor of Cellular Biology in the Franklin College and co-director of the training grant. “We have had many more strong candidates than training slots.”

To address this issue, the new NIH award will double the number of postdoctoral trainees from one to two each year, and matching funding from UGA’s Office of the Vice President for Research will support two predoctoral trainees in addition to the three graduate students supported by the training grant each year.
“This institutional matching support is tremendously important when competing for NIH training grants,” said Dan Colley, CTEGD director, who was the T32 training grant program director for its first 10 years.

Trainees in the program build upon their background in biomedical sciences through specialized courses and research mentored by one or more CTEGD faculty. The program is unique in that students can also broaden their perspective on the global aspects of parasitic diseases through a capstone experience, which typically takes students away from the UGA campus for four to eight weeks. Many of the previous trainees have conducted field studies in a disease-endemic country.

“My capstone experience in Kenya provided an exceptional opportunity to gain experience both working in the field and in a laboratory in a developing setting,” said Briana Flaherty, a doctoral student in the CTEGD and the department of infectious diseases. “This short time has had a profound impact on my future interests and career goals.”

The many international collaborations of the center’s faculty provide a wide variety of opportunities to the trainees. Over the last nine years, graduate students have worked in Haiti, Tanzania, Argentina, Thailand and Kenya. The Office of the Vice President for Research also has committed funds over the next five years to assist in the provision of these experiences on the T32 training grant.

“We in CTEGD are extremely pleased that NIH has seen fit to fund this T32 training grant for an additional five years,” Colley said. “It is an investment in our new program directors, Drs. Striepen and Moreno, and in CTEGD’s commitment to high-quality training of the next generation in this important area of parasitic disease-related research.”

The grant funding is provided under NIH award number 3T32AI060546.

UGA Center for Tropical and Emerging Global Diseases
The University of Georgia Center for Tropical and Emerging Global Diseases draws on a strong foundation of parasitology, immunology, cellular and molecular biology, biochemistry and genetics to develop medical and public health interventions. Established in 1998, the center promotes international biomedical research and educational programs at UGA and throughout Georgia to address the parasitic and other tropical diseases that continue to threaten the health of people throughout the world. For more information, see

Writer: Donna Huber
Contact:Boris Striepen