This story originally published on April 21, 2015 in observance of the COPH’s 30^th anniversary celebration.

Three Distinguished USF Health Professors in the Department of Global Health at the USF College of Public Health – Drs. Tom Unnasch, John Adams and Dennis Kyle – are ranked among the university’s best externally-funded investigators in terms of research dollars, and two are in the top five. A major focus of their research is malaria.

A fourth Global Health professor, Dr. Michael White, published a groundbreaking study just last month that may revolutionize the global fight against malaria.

Unnasch, the department chair, said much of Global Health’s research funding comes from external grants from the National Institutes of Health, primarily the National Institute of Allergy and Infectious Diseases.

The Bill and Melinda Gates Foundation has come through with what he called “a substantial portfolio of funding”: a $4.5-million grant to Adams this year for developing new drugs and researching new genetic targets for malaria.

Kyle and Adams also have established collaborations with the Draper Laboratory to conduct research with artificial livers to study malaria in livers, which also is funded by the Gates Foundation, Unnasch said.

The combination of expertise and generous funding has helped put the department on the global cutting edge and in the thick of international connections that will help keep it there.

“The department is becoming quite well-known now as a research institution for malaria and other vector-borne diseases,” Unnasch said. “We have lots of good collaborations with people in Thailand at Mahidol University, and a lot of collaborations with people in Africa. There’s also quite a bit of contact between our department and people in the mosquito control field here in the state of Florida.”

Unnasch said those include regular work with the Florida Mosquito Control Association (of which Unnasch is on the board of directors), the Department of Health Laboratories, the Florida Department of Health, and various research projects with mosquito control in Hillsborough, Pasco, Manatee, Volusia and St. Johns counties, as well as with the Florida Keys Mosquito Control District in Monroe County.

For mosquito researchers, Unnasch said, the reason is obvious. For everyone else, it might be alarming.

“Florida’s the best place in the country if you want to do research on mosquito-transmitted diseases,” he said. “There are four arthropod-borne viruses, or arbovirus, infections that occur in the United States, and three out of the four are endemic to Florida. That’s why Florida spends $75-100 million a year on mosquito control. Only California spends more.”

Last month, the College of Public Health made headlines as Dr. Michael White, a professor in the College of Public Health’s Department of Global Health and the Morsani College of Medicine’s Department of Molecular Medicine, led a team of researchers that became the first to uncover part of the mysterious process by which malaria-related parasites spread at explosive and deadly rates inside humans and other animals.

As drug-resistant malaria threatens to become a major public health crisis, the findings could potentially lead to a powerful new treatment for malaria-caused illnesses that kill more than 600,000 people a year.

In a study published online March 3 in the high-impact journal PLOS Biology, the USF researchers and their colleagues at the University of Georgia discovered how these ancient parasites manage to replicate their chromosomes up to thousands of times before spinning off into daughter cells with perfect similitude – all the while avoiding cell death.

Malaria caused about 207 million cases and 627,000 deaths in 2012, according to the Centers for Disease Control and Prevention.  About 3.2 billion people, or nearly half the world’s population, are at risk of malaria, according to the World Health Organization.

White said that this study, which he called the first for a USF Health laboratory in publishing original research in PLOS Biology, will help get more potential treatments in the pipeline.

“The more we understand their vulnerability,” he said of the parasites, “the better chance we can keep that pipeline full.”

With the collective efforts and expertise of Drs. Adams, Kyle, Unnasch and White, the USF College of Public Health will remain on the front lines of the fight against one of the world’s most daunting health threats.

Related stories:
USF-led study sheds light on how malaria parasites grow exponentially
New antimalarial drug with novel mechanism of action
Dr. Dennis Kyle receives NIH award to understand extreme drug resistance in malaria
Dr. John Adams leads workshop for Gates Foundation scientists conducting malaria research

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The USF College of Public Health held a celebration and reception on Friday, November 18 to recognize and honor the contributions and work of faculty and staff at their 5, 10, 15, 20, and 30 year service milestones.

Dean Donna Petersen with Dr. Boo Kwa celebrating his 30 years of service at the College of Public Health. (Photo by Ellen Kent)

“Whether we are faculty, staff, administrators or leaders all of us are part of the fabric of the College of Public Health which enables us to do the work that we do. That which helps us grow and improve lives. I’m very proud to be here and incredibly proud of USF Health,” COPH Dean Donna Petersen said.

A tradition for the COPH, the Annual Length of Service Awards, began as a simple gesture in 2009. This year 39 faculty and staff members were honored.

COPH staff enjoying the Length of Service reception. (Photo by Ellen Kent)

“We are all impacted by whatever you do.  Directly from those of us that get to work with you and then indirectly in what you do to contribute to the college,” Petersen said. “I end this day on a very positive and optimistic note for the future because we have great scholars, professionals and champions here to fight for what’s good and right in this community and around the world.”

Congratulations to all employees who celebrated milestone years of service in 2016!

5 Years of Service: Henian Chen, Megan Ditizio, Gabriel Garcia, Patrick Gardner, Benjamin Jacob, Anna Mayor, Manny Mayor, Lisa Mobley, Robert Novak, Donna Rodandello, Renee Salazar, William Sappenfield, Rosemarie Sledge, James Taylor and Min Zhang.

10 Years of Service: Jaime Corvin, Rita DeBate, Sonia Graham, Foday Jaward, Mary Johnson, Dennis Kyle, Anne Marie Little, Jill Roberts and Kate Wolfe-Quintero.

15 Years of Service: Ellen Daley, Anne Gallacher, Thelma Kamman, Steven Mlynarek, Hana Osman and Katherine Small.

20 Years of Service: Marilyn Batchellor, Getachew Dagne, Linda Detman, David Hogeboom, Ellen Kent, Kay Perrin and Jodi Ray.

30 Years of Service: Boo Kwa and Ira Richards.

Click here to view all pictures from the Length of Service Awards.

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The USF College of Public Health aims to focus on the future, as highlighted by Dean Donna Petersen during the State of the College Address on September 26.

“We really need to rein in and be clear about where we’re going, what our direction is and the important things we’d like to do,” she said.

College of Public Health Dean Donna Petersen. (Photo by Anna Mayor)

Petersen highlighted all of the achievements and honors of faculty staff and students from the past year, including Drs. Michael White and John Adams of global health being named distinguished USF professors and Dr. Rita DeBate of health policy and management being named assistant vice-president for health and wellness at USF.

She also highlighted a new approach the COPH is taking in naming Dr. Ellen Daley of community and family health as associate dean for transitional research and practice, to focus on getting students better acquainted with both sides of public health—research and practice.

The first cohort of students exposed to this type of training are doctoral students from across all COPH departments, according to Daley, and have started meeting for weekly seminars.

“Even though someone may be getting their doctorate in epidemiology or in the community and family health focus area, they will understand the big picture of what public health does,” Daley said. “The idea of the cohort is to gain some understanding and greater respect for what other areas do to see the range of what public health does.”

Petersen noted there has been an increase in the number of students enrolled in the DrPH program.

“I know looking at the applicant pool for the DrPH, we are getting outstanding applicants and we’re getting more every year,” she said.

The COPH is also finalizing two new, first in Florida, programs that will be offered to students, the MSPH in genetic counseling and MPH in nutrition and dietetics, and a strengthened master of health administration program, which was fully accredited by CAHME this past year.

Other significant endeavors this year included:

• Six COPH faculty in the Top 20 investigators at USF: Jodi Ray (1), Yehia Hammad (6), Dr. Dennis Kyle (12), Dr. Tom Bernard (13), Dr. John Adams (12) and Dr. Jay Wolfson (20).
• 80 COPH students participating in USF Health’s Research Day including two doctoral student winners: Alison Roth of Global Health and Ngozichukwuka Agu of Community and Family Health.
• The COPH celebrates a 10-year anniversary of working in Panama, providing study abroad experiences for students and participating in cutting-edge research.
• The Lawton and Rhea Chiles Center has broadened its core mission to include women’s health beyond just maternal health on the occasion of its 20^th
• Archivum, the COPH’s electronic business process management system, has been used to streamline academic forms and processes in preparation for self-study and upcoming accreditation.

Petersen also took a moment to recognize the faculty and staff who have earned the CPH designation.

The COPH leads the nation with the number of Certified in Public Health faculty and staff. (Photo by Zack Murray)

“We have more certified faculty and staff than any college or program of public health in the country by far, most people have none,” she said.

In closing, she outlined three items that will be addressed in the upcoming year: investing in faculty, internal and external pressures on financial resources, and upcoming Council on Education for Public Health (CEPH) accreditation.

“You are the heart and soul of our college,” Petersen said to the faculty in attendance.

Of priority for next year is increasing the average median salary of faculty to make them competitive with ASPPH’s latest Faculty Salary Report.

The COPH is also going to streamline efforts to increase enrollment and take steps to prepare for the upcoming CEPH accreditation.

“Our work is cut out for us,” she said. “But, we also set bold goals to continue to excel in our academic, research and community engagement efforts.”

Story by Anna Mayor, USF College of Public Health  

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University of South Florida researchers continue to hone the high-volume screening of compounds that may lead to optimal drugs to combat the rare but deadly infection caused by the brain-eating amoeba Naegleria fowleri.

Distinguished USF Health Professor Dennis Kyle, PhD, who has studied the parasite since the early 1980s, was a featured speaker Sept. 9 at the Second Annual Amoeba Summit in Orlando, FL. The summit brings together health care professionals to spread awareness about risk, diagnosis and the need for research to find effective treatments against primary amebic meningoencephalitis (PAM). The infection is caused by Naegleria fowleri, which flourishes in warm freshwater lakes. Florida, Texas and California are states with the most reported cases of PAM.

Distinguished USF Health Professor Dennis Kyle, PhD, is among a select group of researchers across the country focusing on drug discovery for the rare but deadly infection caused by Naegleria fowleri, commonly known as the brain-eating amoeba. (Photo by Christopher Rice)

Dr. Kyle, a member of the USF College of Public Health Global Health Infectious Diseases Research group, leads a National Institutes of Health-funded study to find faster-acting drugs that might be combined with existing therapies to significantly increase survival rates of patients who contract infections from these pathogenic free-living amoebae. He is among a select group of researchers across the country who focus on this neglected infectious disease.

PAM usually affects healthy children and young adults who engaged in swimming, diving or other water activities that may cause contaminated water to enter the nose.  Once the parasite crosses into the sinuses, the amoeba invades the frontal brain where the infection destroys brain tissue. It kills more than 97 percent of its victims within days. An Orlando teen recently became only the fourth person known to survive an infection by Naegleria fowleri.

The amoeba moves so quickly that by the time doctors definitively identify Naegleria fowleri as the cause of meningitis, it is often too late for existing treatments to work.

“With such a high fatality rate, the odds are likely stacked against any patient who comes into the hospital with this organism,” Dr. Kyle said. “It is very important to develop rapid laboratory diagnostics and drugs that kill the amoeba quicker, so that we have more survivors.”

At the summit, Dr. Kyle highlighted the following approaches that USF is taking to discover a new drug. His laboratory collaborates on different drug discovery projects with Georgia State, USF Chemistry and the Center for Drug Discovery and Innovation, and the biotechnology company Mycosynthetix.

• Working to turn compounds that demonstrate the most promising chemical activity against the brain-eating amoeba into drugs.
• Screening libraries of small molecules and natural products to identify new “hits.” Fungi metabolites have become a promising new source.
• Repurposing drugs that may work against the amoeba — either those approved to treat a different disease or drugs tested in clinical trials but not approved.

USF Health/VA infectious diseases physician Sandra Gompf, MD, with Dr. Kyle at this year’s Amoeba Summit. After Dr. Gompf lost her 10-year-old son to amoebic meningoencephalitis, she and her husband, also a doctor, launched an Amoeba Season awareness campaign to help educate the public on ways to prevent the parasitic infection. (Photo by Christopher Rice)

As they aim to shorten the timeline from discovery of a new drug to treating patients, researchers are also seeking to better understand how the brain-eating pathogen works.

Studies with mice have shown that a microscopic droplet of water containing 1,000 of the pathogenic organisms can cause the same infection as that seen in humans, Dr. Kyle said. But, researchers still don’t know why some people get sick when exposed to the amoeba and others do not.

“Is it the numbers of amoeba, or something about the person’s immune system? Nothing really ties a string between getting infected and not getting infected,” Dr. Kyle said in an interview last month with ABC News Nightline.

For the full ABC News story including comments from Dr. Kyle, click here.

For more on the Amoeba Season campaign, visit www.amoeba-season.com.

Reposted from USF Health News.

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The researchers screened 400 compounds for the Malaria Box project, one of the first open-source drug discovery efforts to combat infectious diseases

The USF Center for Global Health and Infectious Diseases Research was among 55 groups worldwide to participate in a Medicines for Malaria Venture initiative to help catalyze drug discovery for malaria and other neglected diseases. The center is based in the USF College of Public Health.

A paper appearing online today in the journal PLoS Pathogens for the first time describes the results of the organization’s Malaria Box project. The project involved 55 groups, including USF’s, which were provided open access to 400 diverse molecules with confirmed activity against the Plasmodium falciparum malaria parasite. Using a wide variety of biological assays, the researchers screened the commercially available compounds to help select the most promising candidates for further testing in mouse models and medicinal chemistry programs.

From left, Dr. Dennis Kyle, Dr. John Adams and Dr. Rays Jiang, all faculty members based in the USF Center for Global Health and Infectious Diseases Research, used a high-volume screening setup to test compounds in the Malaria Box project.

“One of the most difficult problems with drug discovery is finding a good starting point, a good chemical compound with the potential to lead to a drug,” said Dennis Kyle, PhD, Distinguished USF Health Professor. “In this study collaborators from around the world tested 400 drug and probe-like compounds for multiple diseases and indications to identify essential starting points that will lead to future drugs to treat the most neglected infectious diseases of mankind.”

Dr. Kyle’s laboratory, which can high-throughput screen as many as 7,500 compounds in 72 hours, tested the safety and effectiveness of all 400 compounds against the brain-eating amoeba Naegleria fowleri.

Microscopic image of the brain-eating amoeba Naegleria fowleri

In addition, John Adams, PhD, Distinguished University Professor; Rays Jiang, PhD, assistant professor of global health; and Dr. Kyle profiled Plasmodium falciparum transposon mutant clones with drug-like compounds from the Malaria Box collection. The USF researchers looked for similarities in mechanisms of action with those of artemisinin drugs, the current frontline antimalarial treatments.   The USF researchers’ data analysis, combined with that of other groups, is shared in the PLoS Pathogens publication.

The USF group is now a collaborator in the Pathogen Box project, also spearheaded by the Medicines for Malaria Venture. The project is analyzing a second collection of 400 compounds targeting neglected tropical diseases, including malaria, cryptosporidiosis, leishmaniasis, lymphatic filariasis, onchoceriasis (river blindness), and tuberculosis.

USF participants in the Malaria Box project were, from left, Christopher Rice, postdoctoral student; Beatrice Colon, PhD student; John Adams, PhD, Distinguished University Professor; Yolanda Corbett, PhD, visiting scientist from the University of Milan; Dennis Kyle, PhD, Distinguished University Health Professor; Kenneth Onyeka Udenze, MPH; and Rays Jiang, PhD (foreground), assistant professor of global health.

Reposted from USF Health News

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World Malaria Day is April 25.

“More than 300 million worldwide are sickened by malaria each year, and about one million die,” said Steven Maher, a post-doctoral researcher at the USF College of Public Health. “For most people, the disease causes the individual to be bed stricken for days or weeks and the symptoms are very unpleasant.”

Maher, an alumnus who earned his PhD in global communicable diseases from the Department of Global Health in 2014, has been working on malaria research since his time as a PhD student and decided to continue his research at the COPH as a post-doctoral researcher.

He contributed to the $5.45 million dollar grant USF received from the Bill and Melinda Gates Foundation, to create devices mimicking the human liver in order to analyze the life cycle of the malaria parasite and examine new drugs or vaccines for the Plasmodium vivax and Plasmodium falciparum forms of malaria.

The research team has received an additional four years of funding to continue this research.

“I didn’t want to leave the work unfinished, and it was just starting to get to a level where it could make an international impact,” he said.

In humans, the malaria parasite grows and multiplies first in the liver cells and then in the red cells of the blood, according to the Centers for Disease Control.

Maher and colleagues have become one of the first labs to create a simple, robust liver cell culture system built with a plastic molding technique that they invented and patented.

At present the only way to completely remove all Plasmodium vivax from an individual is to treat with the drug Primaquine, the only approved drug to remove dormant parasites from the liver, according to Maher.

However, Maher notes that Primaquine is toxic to many individuals.

“Future chemoprotection of populations from malaria is dependent on identification of new compounds that kill the dormant parasites,” Maher said. “To find these new compounds, we must use in vitro liver culture techniques, but liver culture is notoriously difficult.”

Image of Plasmodium vivax liver stage parasite at six days post infection. According to Maher, this is the first image ever of a liver stage parasite grown in an in-vitro system taken while the parasite is still alive. (Image courtesy of Steven Maher).

Infecting the liver cultures with Plasmodium vivax and then screening drugs to test if they kill the liver forms of malaria, Maher said his team is on the forefront of this research and is being noticed by the antimalarial drug community.

“We are now beginning to screen potential new drugs provided by both USF and outside developers,” Maher said. “Prior to these advances, drug developers were dependent on rodent animal models to screen for liver stage activity, but rodent models do not accurately predict results in humans.”

Maher and colleagues have also become the first lab to fully troubleshoot the four-week protocol required to perform Plasmodium vivax studies, making it available and practical for other labs to emulate.

The lab is also the first to demonstrate reactivation of Plasmodium vivax dormant forms in in-vitro culture.

Operating out of the Center for Drug Discovery and Innovation (CDDI) and conducting site visits to Thailand, he credits the resources of the COPH with providing him the opportunity to continue advancing his research in this area.

“The CDDI has everything you would want for a drug screening facility, including advanced robotics and imaging systems,” he said. “CDDI has the chemists to provide compounds for antimalarial drug screening, the engineers to help build our screening protocols and systems, and the biological resources, such as access to a well-maintained insectary providing mosquitoes, all in one place to efficiently perform antimalarial research.”

Maher said that drug screening is process-development dependent and that he has found joy in this type of problem solving.

“I want to make a difference,” Maher said. “I appreciate basic research but I would love to retire knowing that the people I meet in endemic countries may one day be aided by our research.”

Going global in the battle against malaria

For Alison Roth, a first year PhD student in the Department of Global Health, her passion for engaging in malaria research grew even more after traveling to Thailand.

“In Thailand, we work with collaborators both at the Armed Forces Research Institute of Medical Sciences and Shokolo Malaria Research Unit who show extreme motivation and dedication to eliminate the burden of those infected,” she said.

Rice fields at research site in Thailand. (Photo courtesy of Alison Roth)

“Here in the U.S. those who are doing malaria-associated research are so removed from the disease that it can be easy to forget what exactly your impact can be,” Roth said. “For me, it is very rewarding to be a part of a project that has capability to greatly influence the discovery of an effective vaccine and ultimately lead to the eradication of this complex disease.”

Working under the direction of Dr. John Adams, distinguished USF health professor in the Department of Global Health at COPH, she’s focusing her research on highlighting the use of novel functional assays that are more realistic to what the malaria parasite encounters upon initial entry into the human host.

“We utilize new methodologies to recapitulate the pivotal period of sporozoite transition from mosquito to human through modifying the in vitro culture microenvironment physically and by exposure to specific biological stimulatory factors; albumin, glucose, calcium, amino acids,” she said. “In collaboration with Dr. Steven Maher and Dr. Dennis Kyle [distinguished USF health professor in the Department of Global Health at COPH], I have applied their novel in vitro human liver model based in micro-device platform to evaluate liver stage development of these conditioned sporozoites.”

Sporozoite is the term used to describe the stage the malarial parasite is in when it lives inside the salivary glands of the mosquito host.

When a mosquito bites a human host, it injects sporozoites at the site and causes the initial infection.

Roth said she’s focusing her research on the use of novel functional assays to simulate key development and transition phases to evaluate potential pre-erythrocytic vaccine candidates.

She is able to screen potential vaccines that target the sporozoite stage of the parasite.

A real-time ‘live’ motility assay tracking the gliding patterns of Plasmodium sporozoites in a controlled environment. (Image courtesy of Alison Roth)

Roth earned her MPH in global communicable diseases from the COPH and said the research exposure she received as an MPH student, as well as the collaborative nature of the COPH affirmed her decision to continue her research efforts here.

“The Global Health Department in the COPH is filled with research labs offering modern technologies and imaging systems that are essential to facilitate my research efforts,” Roth said. “We have access to an Operetta high-imaging content system, Perkin Elmer, which allows for high-throughput processing with precise imaging. Additionally, our location in the IDRB [Interdisciplinary Research Building] building houses multiple core facilities through the CDDI which offer a wide range of services from diverse fields including biology, bioengineering, and chemistry.”

She said her current research findings will also assist to advance future vaccine design and drug discovery.

“We are applying the recent advancements in next generation sequencing to the Plasmodium sporozoite which will be beneficial for future vaccine design and drug discovery,” she said.

The World Health Organization estimates 3.2 billion people, predominately in Africa and southeast Asia, are at risk of malaria, a fact that resonates with Roth.

“Malaria is an important public health issue due to the increase of drug resistance to the top used anti-malarials and no vaccine currently available making the eradication of malaria a difficult task,” she said. “Parasites are a fascinating field and I find the complex life cycle of malaria parasite very intriguing.”

Story by Anna Mayor, USF College of Public Health

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Dennis Kyle, PhD, a Distinguished University Health Professor in the Department of Global Health, USF College of Public Health, was one of six faculty members from USF recently elected 2015 Fellows of the American Association for the Advancement of Science (AAAS).

Dennis Kyle, PhD

Dr. Kyle was honored as part of the AAAS Biological Sciences Section for his distinguished contributions and innovations in the field of global health, especially tropical and infectious diseases. His research interests include elucidation of mechanisms of antimalarial drug resistance and discovery of new anti-parasitic drugs for diverse disease including malaria, visceral leishmaniasis, and primary amoebic meningoencephalitis.

Dr. Kyle has more than 175 publications in the peer-reviewed scientific literature, serves on peer review panels for the National Institutes of Health and chaired the Genomics and Discovery Research Steering Committee and the Compound Evaluation Network for the World Health Organization. He is a fellow of the American Society for Tropical Medicine and Hygiene. His laboratory is supported by research funding from National Institutes of Health, the Bill and Melinda Gates Foundation, and Medicines for Malaria Venture.

After completing a PhD in zoology at Clemson University (1984) and a postdoctoral position at the University of Georgia, he began a 21-year association with the Walter Reed Army Institute of Research. During this time he led key efforts with the U.S. Army’s Drug and Vaccine Development Programs, eventually serving as deputy director of the Division of Experimental Therapeutics. He also served as the chief, Department of Immunology and Parasitology, at the Armed Forces Research Institute of Medical Sciences (AFRIMS) in Bangkok, Thailand (1991-94) and was a senior scientist in the malaria drug program at the Australian Army Malaria Institute (2002-04).

Reposted from USF Health News. Click here for the full story by USF Communications and Marketing.

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A University of South Florida (USF) Center for Global Health & Infectious Diseases Research team has demonstrated a new screening model to classify antimalarial drugs and to identify drug targets for the most lethal strain of malaria, Plasmodium falciparum.

The National Institutes of Health-funded study appeared online Nov. 6 in the journal Scientific Reports.

Half the world’s population is at risk for malaria, a mosquito-borne disease becoming increasingly resistant to the drug artemisinin.

The malaria parasite is becoming increasingly resistant to the drug artemisinin as the front-line treatment to combat the mosquito-borne disease, even though artemisinin is given as a combination therapy with another antimalarial drug.

The USF research provides a better understanding how antimalarial drugs work, thus adding ammunition in the race to overcome the spread of multidrug-resistant malaria – a public health threat that could  potentially undermine the success of global malaria control efforts.

The global health researchers used a collection of malaria parasite mutants that each had altered metabolism linked to defect in a single P. falciparum gene. They then screened 53 drugs and compounds against 71 of these P. falciparum piggyBac single insertion mutant parasites. Computational analysis of the response patterns linked the different antimalarial drug candidates and metabolic inhibitors to the specific gene defect.

This novel chemogenomic profiling revealed new insights into the drugs’ mechanisms of action and most importantly identified six new genes critically involved P. falciparum’s response to artemisinin, but with increased susceptibility to the drugs tested.

“That represents six new targets potentially as effective as artemisinin for killing the malaria parasite,” said the study’s co-senior author Dennis Kyle, PhD, a Distinguished USF Health Professor in the Department of Global Health, USF College of Public Health.  “There is definitely a sense of urgency for discovering new antimalarial drugs that may replace artemisinin, or work better with artemisinin, to prevent or delay drug resistance.”

From left, Dr. John Adams, Dr. Rays Jiang and Dr. Dennis Kyle are members of USF’s Center for Global Health & Infectious Diseases Research team.

The multi-faceted team of USF scientists worked with researchers from the University of Notre Dame’s Eck Institute for Global Health to undertake the chemogenomic profiling of P. falciparum for the first time.

“The methodology used in the study highlights the importance of team-based interdisciplinary research for cutting-edge scientific innovation by combining the tools of drug discovery methods with functional genomics and computational biology analysis. We are very happy to have such an important result published in the first year of a five-year NIH grant,” said co-senior author John Adams, PhD, Distinguished University Health Professor in the Department of Global Health, USF College of Public Health. “Equally important are the enormous efforts by the cadre of talented postdoctoral researchers and graduate students who were critical for making this type of challenging scientific study a success.”

“That interdisciplinary collaboration is where the power of this work comes to light,” Dr. Kyle said. “It helps us develop the tools, the molecular techniques we need to rapidly mine huge amounts of data and to discover new drug targets in ways not previously feasible.”

P. falciparum causes three-quarters of all malaria cases in Africa, and 95 percent of malaria deaths worldwide. It is transmitted to humans by the bite of an infected mosquito, which injects the one-celled malaria parasites from its salivary glands into the person’s bloodstream.

Half the world’s population is at risk of contracting malaria, so any decrease in artemisinin’s effectiveness could result in more deaths.

The USF study was supported by grants from the NIH, National Institute of Allergy and Infectious Diseases (NAID).

Microscopic image of malaria parasite P. falciparum

Article citation:
Anupam Pradhan, Geoffrey H. Siwo, Naresh Singh, Brian Martens, Bharath Balu, Katrina Button-Simons, Asako Tan, Min Zhang, Kenneth O. Udenze, Rays H.Y. Jiang, Michael T. Ferdig, John H. Adams & Dennis E. Kyle. “Chemogenomic profiling of plasmodium falciparum as a tool to aid antimalarial drug discovery.” Scientific Reports, 5, Article number 15930 (2015). doi: 10.1038/srep15930.

Written by Anne DeLotto Baier, USF Health Communications.

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Among the microbes targeted is the brain-eating amoeba Naegleria fowleri

University of South Florida College of Public Health researchers were recently awarded a National Institutes of Health (NIH) grant to identify optimal drug candidates that could ultimately lead to a fast-acting treatment for rare but deadly infections caused by microscopic free-living amoeba (FLA) commonly found in warm freshwater lakes and rivers and in soil. The $425,000 award from the NIH’s National Institute of Allergy and Infectious Diseases is for the first two years of a five-year funding period, which could total $1.7 million over five years.

“Our ultimate goal for this project is to develop at least one new fast-acting drug that could be combined with existing therapies to significantly increase survival rates of patients who contract FLA infections of the central nervous system,” said principal investigator Dennis Kyle, PhD, a distinguished USF Health professor in the Department of Global Health, USF College of Public Health.

Dennis Kyle, PhD, distinguished USF Health professor, with research team members Christopher Rice, PhD, and Beatrice Colon, PhD candidate.

Dr. Kyle’s team will work with David Boykin, PhD, professor of chemistry at Georgia State University, who makes the antimicrobial compounds that USF is developing.

The new grant will build upon previous NIH-funded work by the USF researchers, who have already zeroed in on two new chemical compounds 500 times more potent than existing drugs used to combat the almost always fatal infection caused by the brain-eating amoeba known as Naegleria fowleri.  The new study will expand the screening and development of the most promising drug candidates to target Acanthamoeba spp, as well as Naegleria fowleri.

Naegleria fowleri causes primary amoebic meningoencephalitis (PAM), a rare disease that kills more than 97 percent of its victims within days. PAM is usually contracted by healthy children and young adults who engaged in swimming, diving or other water activities that may forcefully push contaminated water up the nose.  Once in the nose, the amoeba moves quickly to the brain where the infection destroys brain tissue.

Excerpts from USF Health News. Read the full story here.

Related media:
Family’s plea: Be aware of amoeba dangers
Brain eating ameoba [VIDEO]

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Potent compound inhibits protein synthesis at various stages of malaria parasite’s life-cycle

With the rapid emergence of multi-drug resistant strains of malaria, the need to find new drugs capable of delaying or preventing drug resistance has become even more urgent.

Now, an international team of researchers – including two from the University of South Florida – has discovered a promising new antimalarial drug that inhibits the production of a protein involved in the replication and transmission of the malaria parasite.  If successfully developed, the new drug working in combination with an existing fast-acting antimalarial may be less likely to develop rapid resistance to major strains of malaria parasites.

Dennis Kyle, PhD, Distinguished University Health Professor, and Anupam Pradhan, PhD, a research associate, both from the USF College of Public Health Department of Global Health, were among the co-authors of the multisite preclinical study published June 18 in the journal Nature.  The study was led by researchers at the University of Dundee Division of Biological Chemistry and Drug Discovery.

Dennis Kyle, PhD

The USF researchers demonstrated in a mouse model of malaria that the new drug candidate, known as DDD107498, helped block the spread of the parasitic disease with greater effectiveness than current antimalarial combination drugs. Their work was supported by a grant from Medicines for Malaria Venture.

In various preclinical studies the potent drug proved highly effective and safe while demonstrating a broad spectrum of antimalarial activity against several life-cycle stages of the malaria parasite Plasmodium falciparum.  This ability to kill parasites without harmful or bothersome side effects at all stages of a complex malaria lifecycle – after the parasites enter the bloodstream through the bite of bloodstream, once they infect the liver and as soon as the modified parasites emerge from the liver to attack red blood cells – will be critical in eradicating malaria.

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