Tag: Drug Discovery

Southern Research at 75: Discovering cancer drugs and extending lives

Posted on November 2, 2016

Southern Research scientists have been attacking cancer since the organization’s early days, developing successful approaches to chemotherapy, screening biological agents that kill cancer cells, and making other advances.

A key contribution to this fight involves the organization’s track record for discovering FDA-approved anticancer medicines.

“Of the 200 or so drugs currently used to treat cancer, seven were discovered at Southern Research,” Dr. Francis Collins, director of the National Institutes of Health, said in a video message to mark the Birmingham-based non-profit’s 75th anniversary in October.

Southern Research dacarbazine
Dacarbazine became Southern Research’s first FDA-approved cancer drug in 1975.

Collins noted that two of Southern Research’s cancer drugs are on the World Health Organization’s List of Essential Medicines, indicating their critical importance to oncology. They are fludarabine, a treatment for chronic lymphocytic leukemia (CLL), and dacarbazine, used against malignant melanoma and Hodgkin’s lymphoma.

“At Southern Research, we have developed seven anticancer drugs and made critical advances in basic research that have deepened our understanding of cancer,” said Art Tipton, Ph.D., the organization’s president and CEO.

“We will continue to use our deep science and development tools to work toward novel treatments for a disease that kills a half million Americans each year,” he added.

Southern Research’s first anticancer drug, dacarbazine, received FDA approval in 1975 and remained a front-line treatment against melanoma for many years. Its seventh FDA-approved drug, pralatrexate, entered the market in 2009 as a treatment for aggressive blood cancers.

EXTENDING LIVES

The road to FDA approval is long, as the timeline for pralatrexate demonstrates.

Research on drugs in this class began in the 1950s at California’s SRI International. A partnership between Southern Research, SRI and New York’s Memorial Sloan Kettering led to clinical trials on related compounds beginning in the 1980s.

SR 75th_Logo_Horz_RGBOnce pralatrexate was identified as viable clinical candidate, it was licensed to Allos Therapeutics for additional development in 2002. FDA approval for pralatrexate (brand name: Folotyn) as a treatment for peripheral T-cell lymphoma came in 2009 – six decades after the initial research began.

“We prepared and tested many compounds before finally identifying a substance that gave favorable results,” Southern Research organic chemist Robert Piper said at the time. “We are very glad our compound will help alleviate human suffering and extend lives.”

Piper’s role was to synthesize quantities of high-purity pralatexate used in preclinical investigations.

Piper was also involved in the discovery of amifostine, an FDA-approved medicine that protects patients from harmful effects associated with radiation treatment and chemotherapy.

THE ‘DREAM TEAM’

The foundation of Southern Research’s success in drug discovery was laid in the 1950s, when the organization assembled what former CEO Jack Secrist, Ph.D., has called the “Dream Team” in cancer research.

Under the overall direction of Howard Skipper, the leadership team was composed of John Montgomery, Frank Schabel and Lee Bennett, who headed the Organic Chemistry, Chemotherapy and Biochemistry departments at Southern Research, respectively.

“They worked together for many years, and together with their staff, were a very effective team,” Secrist said in an interview.

Southern Research cancer team
The Southern Research ‘Dream Team’, from left, Frank Schabel, Lee Bennett, Howard Skipper, and John Montgomery.

The Southern Research team established an efficient and effective approach to the development of potential new drugs, he said.

“New compounds were evaluated rapidly, and those with potential were subjected to more detailed evaluations as soon as possible, and compounds that had no activity or weak activity were set aside to make way for new compounds,” said Secrist, who once headed Southern Research’s Drug Discovery division.

This approach to drug discovery is still in use at Southern Research today, he added.

The contribution of Montgomery, a member of Southern Research’s cancer team for more than 40 years, was particularly significant. He was involved in the discovery of five FDA-approved anticancer drugs: lomustine, carmustine, dacarbazine, fludarabine, and clofarabine.

“This is what we all aspire to as drug discovery researchers, moving life-saving compounds from conception to clinic,” said Secrist, co-inventor of clofarabine with Montgomery.

Read a story about how clofarabine helped save the life of a teenage leukemia patient.

 

This is Part Nine of a series looking at the history of Southern Research.

Southern Research at 75: Targeting HIV/AIDS for 30 years

Posted on October 27, 2016

Southern Research scientists joined the front lines in the battle against HIV/AIDS in 1986, not long after the deadly viral infection emerged as a terrifying new public health threat in the United States.

Southern Research HIV/AIDS
HIV infection has been blamed for 35 million deaths across the globe.

Three decades later, the Birmingham non-profit organization is deeply involved in a broad-based initiative to find a cure for HIV infection, which the World Health Organization has blamed for 35 million deaths globally.

Scientists at Southern Research’s research center in Frederick, Maryland, are working to develop and standardize testing assays that will help researchers detect the hidden remnants of HIV in patients successfully treated with antiretroviral medications.

These hiding spots are called “latent reservoirs,” and they allow the virus to lurk unseen for years even though blood tests no longer show traces of HIV. Because the virus is not eradicated from these cellular havens, it can spring back into action when drugs are stopped intentionally or unintentionally, triggering a full-blown infection.

“In the U.S. and other developed countries, because of the availability of highly effective antiviral therapies, the virus is completely suppressed, and HIV-infected people are leading essentially normal lives. However, they still harbor the virus,” said Mike Murray, Ph.D., director of government business development for Southern Research’s Drug Development division in Frederick.

“The next step in the fight against AIDS is the cure,” he added. “The question is how do you go in and get rid of the virus completely?”

 SR 75th_Logo_Horz_RGBTo support researchers searching for that cure, Southern Research is working to expand access to what’s called the Quantitative Viral Outgrowth Assay (QVOA). Though expensive and labor intensive, the QVOA is considered the most effective testing platform for HIV/AIDS researchers trying to evaluate the latent viral reservoir.

Southern Research is also working with experts in HIV latency to develop alternative assays that are quicker, more sensitive and less costly.

TARGETING VIRAL THREATS

Southern Research’s current HIV/AIDS work builds on decades of experience in the field of viral threats.

The organization’s virus research program got started in the 1950s, and early work focused on herpesviruses, poxviruses and mosquito-borne viruses such as Yellow Fever. In the 1970s, Southern Research virologists evaluated potential drugs against the Gross murine leukemia virus, a retrovirus that causes cancer in mice.

In 1986, the organization’s Microbiology-Virology department began work on a U.S. Army contract to study antiviral activity of compounds against exotic RNA viruses.

That same year, the Army and the National Institutes of Health (NIH) asked Southern Research to evaluate compounds for the treatment of AIDS, caused by the human immunodeficiency virus, a retrovirus that has RNA as its genetic material.

Before long, Southern Research was testing 1,500 compounds a year, making it one of the first laboratories outside the NIH evaluating AIDS compounds on a major scale.

The earlier testing program on the Gross leukemia virus, along with the development of new assays for large-scale screening, prepared Southern Research to greatly expand evaluation of potential HIV/AIDS compounds. Its labs were eventually testing large numbers of synthetic chemical compounds advanced for screening against the virus, resulting in around 20,000 tests annually for a decade.

Southern Research’s anti-HIV screening program became the largest in the country, and many of the AIDS treatments now on the market were evaluated through its program.

SEEKING NOVEL TREATMENTS

Southern Research HIV/AIDS
The infectious disease labs at Southern Research began working on HIV/AIDS in 1986.

Over the years, Southern Research’s efforts against HIV/AIDS have moved forward on several fronts, based on longstanding partnerships with the National Institutes of Health and other government agencies.

In 2014, the organization received a $24 million contract from the Division of AIDS (DAIDS) at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to provide drug discovery and development services that could lead to potential new drugs for the treatment and prevention of HIV infection.

Using high throughput screening, an automated process that rapidly assesses the activity of drug-like compounds, and preclinical studies, Southern Research scientists are seeking to identify and develop novel antiretroviral molecules against HIV.

Their focus is on therapeutics for novel viral targets not inhibited by current therapies and topical microbicides, which could neutralize the virus prior to infection.

The latent reservoir work now being done for DAIDS-NIAID puts Southern Research back on the front lines in the effort to prevent, treat, and find a cure for HIV infection, which produces around 40,000 new cases in the U.S. each year.

 “We are excited to be contributing to the HIV Cure Initiative,” said Murray, who previously headed infectious disease research for Southern Research in Frederick.

 

This is Part Eight of a series looking at the history of Southern Research.

NIH director thanks Southern Research for ‘treatments, cures and real hope’

Posted on October 14, 2016

In a message to mark Southern Research’s 75th anniversary, Dr. Francis S. Collins, director of the National Institutes of Health, praised the organization’s scientists for making significant advances against cancer and other diseases.

“Since 1941, Southern Research has made advances that have helped people all across this country – in fact, all around the globe,” Collins said in a video shared with the Birmingham-based non-profit.

In particular, the leader of NIH, the nation’s chief medical research agency, noted the achievements of Southern Research’s long-standing cancer research program. The organization’s scientists played key roles in developing effective chemotherapy methods and in the discovery and development of numerous FDA-approved oncology treatments.

“Of the 200 or so drugs currently used to treat cancer, seven were discovered at Southern Research,” Collins said. “In fact, two of them – fludarabine and clofarabine – are even on the World Health Organization’s list of essential medicines.”

In addition, Southern Research has provided vital research tools and models that allowed other scientists to advance the development of cancer therapeutics, he said.

TARGETING DISEASES

While efforts to discover new oncology drugs continues at Southern Research, Collins noted that its scientists are also working on potential therapeutics for Alzheimer’s, Parkinson’s, diabetes, Lou Gehrig’s disease, and tuberculosis, among others.

At the same time, Southern Research is helping researchers around the world test new disease-fighting strategies. “The area of HIV/AIDS research has been a real standout,” he said.

Collins singled out Southern Research’s work in the field of reproductive toxicology, which seeks to prevent birth defects, and on the Zika virus, which has suddenly emerged as a serious threat to public health around the world.

Collins also responded to a letter from Southern Research CEO and President Art Tipton, Ph.D., who thanked the NIH for providing the Birmingham non-profit with more than $500 million in funding over the past three decades.

“Mr. Tipton, I want to let you, along with all of Southern Research and its supporters, know that you are indeed welcome,” Collins said. “And on behalf of the NIH and the American taxpayer, I want to thank you, Southern Research, for a tremendous return on this investment – a return measured in treatments, cures and real hope for a better future for people all around the world.

National Cancer Institute extends toxicology contract with Southern Research

Posted on October 5, 2016
NCI extends long-term toxicology contract with Southern Research.
NCI extends long-term contract with Southern Research for preclinical toxicology screening of cancer drugs.

Southern Research has been awarded a five-year IDIQ contract with a potential value of $19 million from the National Cancer Institute (NCI) to study the preclinical toxicology of new drugs under development for the treatment of cancer — contract number HHSN261201600018I.

The contract is one of three ongoing contracts between Southern Research and the NCI, and has been in place continuously since 1979. This is the latest in a series of contract extensions for the organization.

The two additional ongoing contracts between Southern Research and the NCI are for research on the pharmacology of potential new cancer drugs, and for evaluation of drugs intended for the prevention of cancer.

“Our ultimate goal with this contract is to help the NCI develop an understanding of how different drug candidates interact with and affect living systems,” said Charles Hébert, Ph.D., senior program leader and principal investigator on the project for Southern Research. “The collection of this information is necessary so the FDA can determine whether a particular drug candidate is safe for clinical trial testing in humans.”

Toxicology testing is an integral part of the drug development process. In order to determine the safety of a new drug candidate, researchers must first conduct dose range-finding studies to establish the maximum tolerated dose, and to aid in the selection of dose levels for use in further testing.

Once the appropriate dose range has been established for the selected species, larger and more detailed definitive studies are conducted. Those definitive studies differs from dose range-finding studies in that they require deeper and more thorough analysis of the ways a particular drug may affect animals, and by extension, humans. Ultimately, the definitive studies provide key information that is used by the FDA to determine the recommended dose options for any drug candidate approved for clinical trial.

“Southern Research has been at the pioneering forefront of cancer research for more than 70 years, and we are particularly proud of our work with the National Cancer Institute,” said Art Tipton, Ph.D., president and CEO of Southern Research. “We have invested heavily to develop unique capabilities and institutional knowledge in this field, and work diligently to stay on the forefront of the field enabling us to improve people’s lives by finding cures to some very challenging diseases.”

Clofarabine co-inventor Jack Secrist talks about drug discovery

Posted on September 30, 2016

Drug discovery researchers like Jack Secrist are motivated by a strong desire to see their work save lives and make a profound difference.

Secrist, the former head of Drug Discovery at Southern Research, is co-inventor of clofarabine, a drug approved by the Federal Drug Administration in 2004 for acute lymphoblastic leukemia (ALL) in pediatric patients like Frances Grace Hirs.

Frances Grace was battling a third bout of ALL in 2013 when she was treated with clofarabine, which helped put her on the road to recovery. (Read a story about her treatment.)

clofarabine-poster“This is what we all aspire to as drug discovery researchers, moving life-saving compounds from conception to clinic,” Secrist said in 2005, shortly after clofarabine received FDA approval.

In a new interview, Secrist talks about how he and his Southern Research colleagues discovered clofarabine and how the drug moved along to the path to become the first treatment for childhood cancer approved by the FDA in more than a decade.

In this Q&A, Secrist also shares his views on how Southern Research, which has discovered seven FDA-approved drugs used in cancer treatment, has been able to consistently develop new therapies that address unmet medical needs.

Southern Research was visited recently by Frances Grace Hirs, who was treated with clofarabine after a second leukemia relapse. Her parents credit the drug with stabilizing her condition, making a bone marrow transplant possible. As a co-inventor of the drug, do you hear stories like this often?

Secrist: In my experience, at least as it pertains to chemists who are inventors of cancer drugs that end up being FDA approved, it is rare that you would meet someone who had benefited from the drug unless it happens to be a family member, friend, or acquaintance. The inventors are far removed from both the oncologists who select the drugs and the patients who take them.

Southern Research Secrist
Clofarbine co-inventor Jack Secrist

In this situation, I can relate two stories. I did meet a father and a daughter who had benefited from the drug in Birmingham, and they were focused on making sure that others who might benefit from the drug would be appropriately informed.

The other time that I saw patients who benefited from the drug was at the FDA hearing where the drug was approved. A father brought his son to the hearing and he took advantage of the public forum to relate the story of his son and how this drug has certainly saved his life. He was holding the boy, who was perhaps five or six, in his arms as he spoke. It was a moving scene.

How did the work that led to clofarabine get started?

Secrist: This question is somewhat more technical, but I will provide some information about how we moved toward the drug that became clofarabine. First, we were working in the nucleoside area, looking for drugs that would affect DNA function in cancer cells, which was at the time the best way to develop a new cancer drug. We chose to work on nucleosides since they are the building blocks of DNA, and we felt that finding something that would be recognized by the cancer cells, and perhaps have selectivity, was more likely in this area.

At the time, around 1983, we had funding from National Institutes of Health (NIH) in the form of what is called a program project grant to search for new drugs in this area, and to evaluate them in biological systems. There were two potential drugs that looked promising at the time that were nucleosides, and we had the detailed biological data to be aware of structural concerns with both drugs.

John Montgomery (an organic chemist and key member of the cancer research team) and I then formulated a plan to make a series of new compounds that would be similar enough that they might have activity, but would have structural changes that would overcome the concerns we saw with these two potential drugs. We made this series of compounds, and the end result was clofarabine.

By the way, both of the other compounds also became FDA approved: one of them is fludarabine and the other is cladribine. Interestingly, the three compounds, though very similar in structure, are used for different forms of leukemia.

Can you recount any significant developments or insights that occurred during your work on this project?

Secrist: The first insight that we developed, which really was just a confirmation of what we already felt, was that very small changes in the structure of a molecule can result in very large changes in biological and clinical activity. The utility of clofarabine, fludarabine and cladribine is a clear demonstration of that fact, and it can be seen in other areas, as well.

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Secrist

Another insight that was strengthened was that the more robust the biological (anticancer) data is on a compound, the more likely it is to become FDA approved. Compounds with some activity and selectivity, but not really strong data, most likely will not make it through to approval. Clofarabine had very strong data supporting its move into clinical trials.

It is also true, by the way, that there is not a connection between what human tumors a potential drug can cure in model systems and what tumors it may cure in humans. It would be wonderful if that was the case, but at least with the current models no such correlation exists. Again, we get back to the fact that robust activity and selectivity data across a wide range of tumor types is the best indicator.

When clofarabine received FDA approval in 2004, it was the first new pediatric leukemia to hit the market in more than a decade. How would you assess its significance?

Secrist: Thinking back to the clinical development of the drug, which started at M. D. Anderson Cancer Center in Texas, there was a critical chance happening. A family had a child who had gone through the available drugs for his leukemia, and he was not responding. They asked to be able to try clofarabine, which was not yet available for trials, and their request was granted. The child responded immediately, and the family was truly grateful.

That chance happening suggested the best path to approval, that is, through a focus on childhood leukemia, though there were of course adult trials as well. The drug clearly helped children, and the FDA was very interested in finding a new drug for childhood cancers, and they were very helpful and supportive.

When the ODAC (Oncology Drug Advisory Committee), a group of outside clinicians, voted for approval, the FDA was really pleased to have the first new drug to treat childhood cancers in more than a decade.

Southern Research has discovered seven drugs used in cancer treatment. What made the organization such a hotbed for the discovery of anticancer drugs?

Secrist: In considering why Southern Research was so successful in developing new cancer drugs, I believe that there are a number of reasons. First, we had extremely talented scientists who were dedicated to the development of new drugs that would be useful in the treatment of cancer. The Dream Team in that regard comprised Howard Skipper, John Montgomery, Frank Schabel, and Lee Bennett. They worked together for many years, and together with their staff, were a very effective team.

Southern Research cancer team
The Southern Research ‘Dream Team:’ from left, Frank Schabel, Lee Bennett, Howard Skipper, and John Montgomery.

Second, that team developed an efficient and effective approach to the development of potential new drugs. New compounds were evaluated rapidly, and those with potential were subjected to more detailed evaluations as soon as possible, and compounds that had no activity or weak activity were set aside to make way for new compounds. This iterative approach to drug discovery is still in use today, though the biological systems have evolved over the years.

Finally, in the early years the Dream Team had not only their own ideas on the type of compounds to pursue in the search for new cancer drugs, but also the input of the cancer research team at the NIH. Thus, Southern Research scientists had access to the latest information available to NIH, including areas of activity, clinical results, and evaluation model advances.

In the early years Institute scientists would go up to NIH to present results, and would of course hear presentations about the results of others. In later years we used scientific meetings and personal contacts to gain that information. The result was an ability on our part to look in more fertile fields for new cancer drugs.

 

Southern Research hires VP of Quality and Compliance

Posted on September 14, 2016

Southern Research is pleased to announce the hiring of Greg Furrow as Vice President of Quality and Compliance. As vice president, Furrow joins the executive team, and in addition to overseeing quality and regulatory compliance, will have oversight of environmental health and safety (EH&S) standards across all of Southern Research.

Prior to joining Southern Research, Furrow served as Vice President of Quality and Regulatory Compliance at WIL Research, where he was responsible for all areas of compliance and EH&S across six laboratories in the United States, France and the Netherlands. Furrow is also a board member and past-president of the Society of Quality Assurance (SQA), and is active in the quality assurance community globally.

“We are excited for Greg to join Southern Research, and look forward to the contributions he will make across our organization,” said Art Tipton, Ph.D., president and CEO of Southern Research. “Our scientists and engineers come to work every day prepared to help solve some of the world’s hardest problems, and the quality of our work and compliance to regulatory standards is of the utmost importance. This move further streamlines communication on safety issues directly to the executive team, and will strengthen our organization more broadly.”

Early Career

After receiving a master’s degree in analytical chemistry at the University of Maryland, Furrow started his career as an analytical chemist at the USDA, then with Eli Lilly and Company, where he worked for 21 years. He left the bench to oversee the company’s analytical laboratories at their Clinton Laboratories manufacturing site. This transition opened the door to a management position in human resources for global Toxicology and Drug Disposition, and ultimately a position as Manager of Quality Assurance for Global Toxicology & Drug Disposition and global Elanco nonclinical and clinical.

“Like a lot of other things, management is all about people,” Furrow added. “My role is to ensure that the people who are working in the lab are empowered with the knowledge and resources they need to be successful and accountable. I am excited to bring my expertise in the field to lead this function and work as a team to accomplish our quality and compliance goals.”

In 2006, Furrow left Eli Lilly to lead a segment of Regulatory Affairs and Quality as a senior director with Charles River, based in Shrewsbury, Massachusetts. In this role, he spent five years expanding his focus and deepening his understanding of the quality and safety standards involved with industrial chemicals and new devices.

Quality and Compliance as a tool

“I have always approached quality assurance from the position that we are not the police,” Furrow said. “The key to any successful operation is to change the perception from one where QA is the watchdog, to one where QA is a valued partner available to offer insight, feedback and guidance. Southern Research has a distinguished reputation for high quality work, and I look forward to working with teams to harmonize QA, improve quality and efficiency across the entire company and empower individuals to take ownership of their processes and improve performance.”

A past-president of the SQA, Furrow remains active in the global QA field. Additionally, he is co-chair of the committee tasked with writing a response to the GLP Notice of Proposed Rulemaking (proposed revision to the FDA GLP regulations). Furrow also has a deep appreciation for the importance of environmental health and safety and will bring an experienced viewpoint as the new leader for this critical function.

At the end of the day, it’s all about the people. For the past 75 years Southern Research has empowered its people to drive innovation within the state, region and for a global clientele. Furrow will strengthen this tradition while continuing to influence policy and advancing best practices that will lead to future scientific discoveries.

NIAID contracts with Southern Research to study Zika

Posted on July 14, 2016

Southern Research has received a contract from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) to expand their research on the Zika virus (ZIKV). The award is for an initial $901,048, with a possibility of increasing up to nearly $3.9 million over the next two years, in accordance with Contract No. HHSN2722010000221.

The funds have been awarded for the development of a non-human primate model of ZIKV infection for product evaluation. Research will involve evaluating the pathogenicity of three different geographic isolates of ZIKV at increasing concentrations, and assessing the impact of prior exposure on immunity to subsequent infection with the same isolate, or a different isolate of the virus. The resulting model will serve as a resource to inform research around possible vaccines or therapeutics for ZIKV disease.

“Our ultimate goal with this project is to establish a model of Zika virus infection that can be used for the evaluation of new vaccines and therapeutics in optional efficacy studies sponsored by NIAID,” said Jonathan Rayner, Ph.D., principal investigator on the project, and head of infectious disease research, Drug Development, at Southern Research. “There is an understanding that the virus may continue to spread into new regions over the summer. Therefore, this contract from NIAID is timely and will help us to expedite efforts to understand the pathogenesis of this virus, and support the search for new vaccines and therapeutics.”

ZIKV is spread primarily through the bite of an Aedes aegypti or Aedes albopictus mosquito, but can also be transmitted sexually. An outbreak of the virus in Brazil and South and Central America has led to a significant increase in the number of children born with microcephaly, and has caused the Centers for Disease Control and Prevention to issue travel warnings to pregnant women and others considering travel to regions where the virus has spread. With a growing number of confirmed ZIKV cases in the United States, there is no known vaccine or treatment for the virus.

“Southern Research has a long history of pivotal work on infectious diseases, including mosquito-borne illnesses including dengue, chikungunya, and West Nile Virus,” said Art Tipton, Ph.D., president and CEO of Southern Research. “Our team is uniquely positioned to support the growing body of global research on the Zika virus through translational science, and we’re grateful for the solid partnerships we’ve developed over the years with the NIH and NIAID.”

The research will be led by Jonathan Rayner, Ph.D. in collaboration with Senior Project Leader Fusataka Koide, Ph.D. In addition to the non-human primate model that is the subject of this contract, Southern Research is working on other in vitro and in vivo models for ZIKV, and has previously developed a unique antiviral assay used by researchers to screen candidate therapeutics and a mouse model to evaluate the efficacy of those therapeutics. This research will also provide the foundation for Southern Research to utilize its expertise in Developmental and Reproductive Toxicology to better understand the impact of ZIKV infection on the fetus during pregnancy.

About Southern Research
Southern Research is a not-for-profit 501(c)(3) research institution with nearly 500 scientists and engineers working to solve some of the world’s hardest problems across four key divisions: Drug Discovery, Drug Development, Engineering, and Energy & Environment. Founded in 1941, 2016 marks Southern Research’s 75 Anniversary. Over this time, the institution built a trusted name for itself, and has continually worked with some of the world’s leading organizations, including the National Cancer Institute, National Institutes of Health (NIH), the U.S. Department of Defense, the U.S. Department of Energy, NASA, several major aerospace firms, the nation’s largest utility companies, and other private and government organizations. Headquartered in Birmingham, Southern Research has additional laboratories and offices in Wilsonville and Huntsville, Alabama; Frederick, Maryland; Durham, North Carolina; Cartersville, Georgia; and Houston, Texas. For more information, please visit www.SouthernResearch.org.

Brazilian intern joins SR to study Zika virus

Posted on July 6, 2016

Throughout our 75 year history, Southern Research has worked to empower interns, women and people of diverse backgrounds to succeed in the sciences and we are proud of the hard work and unique story of our summer intern, Rafaela “Rafa” Medeiros. Originally from Brazil, Rafa joined our Infectious Disease Research team in Frederick, Maryland from North Dakota State University in Fargo, and will be analyzing ZIKV samples for clues that may help lead to a vaccine.

Rafaela Medeiros analyzing Zika samples in the lab
Rafaela Medeiros (left) and senior biologist Beth Snyder (right) working in the Infectious Disease Research lab.

We sat down with Rafa to learn more about her unique story.

Tell us a little about where you’re from.

I’m from Natal. It’s a coastal city located in northeastern Brazil, in the state of Rio Grande do Norte.

(Note: Natal is the capital city of Rio Grande do Norte, and was a host city for the 2014 World Cup. It is also one of the cities where the Brazilian Zika outbreak was first noticed in 2015.)

And, what do you study?

I completed my undergraduate studies in Biomedical sciences in Brazil, and am currently in the second year of a Masters in Public Health with an emphasis in Management of Infectious Diseases at North Dakota State University in Fargo, North Dakota.

What brought you to Southern Research?

I’m actually here because a former professor of mine, Nathan Fisher, introduced me to Southern Research, and recruited me to work on Zika with the infectious disease research team in Frederick, MD.

I first met Dr. Fisher when I was was in Fargo interviewing for the MPH program. We discussed the possibility of me applying for the Cellular and Molecular Biology Ph.D. program at NDSU, but he has since left and taken a position with Southern Research in Frederick, MD.

As I began my search for internship opportunities, I contacted Dr. Fisher because he knew my background, research interests and capabilities. I’ve been interested in Zika since coming to the U.S. for my program in 2015, but did not know of Southern Research’s work on the virus. So, Dr. Fisher surprised me by introducing me to the team and providing me the opportunity to join the global fight against Zika through this internship.

The work is very important to me because of the impact Zika has had on the region of Brazil where I am from.

What are you working on, specifically?

The internship is a 10 week program, so I’m working to get as much experience as I can. Right now I’m exploring the similarities and differences between two different strains of the Zika virus — African and Asian — and how both strains replicate in vitro.

This means, I’m exploring how the Zika virus replicates in human neuronal cell tissue so that we can get a better understanding of the exact mechanisms of how this virus affects neural tissue.

The research we’re conducting is exploratory in nature, but the Infectious Disease Research team at Southern Research has already made significant progress on a number of assay models that I am getting to learn about.

Rafa at the microscope analyzing zika samples with Beth Snyder.
Rafa at the microscope analyzing samples with Beth Snyder (right).

As a Brazilian, what are your personal thoughts about how the Zika virus is affecting your country?

This is obviously a very hard thing for Brazil, and this outbreak comes at a very difficult time given the state of our government and the lack of funding available for research. But, there are a lot of great people working to fight this virus, both in Brazil and around the world. As a future public health professional, I would love to see our work at Southern Research lead to a vaccine or future eradication of Zika.

What are your career goals?

Research. I’ve always wanted to be a scientist, and my ultimate goal is to help people and make an impact in the community.

As we’re seeing with Zika, research plays a tremendously important role in helping combat the break of an infectious disease, or other major public health crisis. So, my goal is to continue doing research, and stay on the frontline of trying to fight outbreaks, while making a difference in the world.

What do you enjoy doing outside of work?

I’m crazy about movies, books and theater — I was very involved in theater since I was a young girl and it helped me overcome my fear of public speaking. I also love traveling and sports, especially Marta! She’s broken so many barriers for Brazilian women soccer players.

(Note: “Marta” Vieira da Silva was named FIFA World Player of the Year a record five consecutive times, beginning in 2006, and in 2015 she set World Cup record with her 15th career goal.)

Southern Research has a long history of working to empower women and people of diverse backgrounds in STEM careers. What advice do you have for young women who are considering going into science?

Stay focused and believe in yourself.

I always knew I wanted to come to the U.S. to study, and it wasn’t easy, but I jumped at the first opportunity I had. The trick for me was having supportive friends and family. When times got hard, they helped me stay grounded and remain focused on reaching my goals. Life and science can be hard, so it’s important to always believe in your own abilities to succeed.

 

What to know about Zika virus transmission

Posted on June 24, 2016

With mosquito season upon us, here are some facts about how the Zika virus is transmitted so you can take the necessary precautions to protect yourself and stay healthy during your summer travels.

The most common method of transmission is through the bite of an Aedes aegypti or Aedes albopictus mosquito. However, Zika can also be transmitted sexually from an infected man to his partners.

In order to carry the Zika virus, a mosquito must first draw blood from a human or animal that is already infected. Once a mosquito comes in contact with the virus, however, she can pass it along to other humans through the saliva she secretes when biting — this is the same chemical that irritates human skin and can leave welts.

The average lifespan of a mosquito is approximately two weeks. During this time, an infected mosquito may bite several people and can spread the virus with each bite. This process is compounded as the number of mosquitoes in a given area is increased.

Once a human is infected, he or she is most at risk of spreading the virus during the first two weeks of infection. After this time, the virus usually subsides and most people will develop an autoimmunity to be protected from future infections.

It’s important to know: not everyone who has Zika will experience symptoms. However, the most common symptoms are fever, rash, joint pain and conjunctivitis (red eyes). There is also a rare chance of contracting a more severe condition like Guillain-Barré Syndrome.

Therefore, take proper precautions to protect yourself from becoming infected or contributing to the spread of the virus:

Wear protective clothing: Long-sleeved shirts and pants help protect your skin from exposure to mosquitoes. You can also spray your clothes with insect repellant, or for extra protection, treat your clothes with permethrin.

Use insect repellant: Be sure to look for active ingredients including DEET, PICARIDIN, IR3535, OIL of LEMON EUCALYPTUS, and PARA-MENTHANE-DIOL.

Remember, daytime is the most dangerous: A. aegypti and A. albopictus are aggressive daytime biters, so take proper precautions and be aware that these mosquitoes also like to live indoors.

Zika and Sexual Transmission
Men are the only ones who are able to pass the Zika virus to their sexual partners. According to the World Health Organization (WHO), if a man has been diagnosed with Zika, or has experienced Zika-type symptoms, he should abstain from sex or wear condoms for up to six months. Women cannot transmit Zika through sex.

Additionally, any individual who has travelled to areas where the virus is spreading is advised to abstain from sex, or use a condom for eight weeks after travel.

For more information, visit the CDC website on Zika and sexual transmission.

Zika and Pregnancy
Zika virus can have a damaging effect on the development of a fetal neural system if a pregnant woman is infected during the early stages of her pregnancy. According to a recent study published by researchers from Harvard and the CDC, a woman infected by Zika during her first trimester is shown to have a 13 percent risk that the child will develop microcephaly.

This same study found “negligible” risks for women infected with the virus late in second or third trimesters. To date, there are no reports of Zika being passed to infant children through breastfeeding. More research is needed before the health community is able to make a definitive statement about the risks associated with microcephaly or other birth defects.

For more information about Zika and pregnancy, visit the CDC page for Pregnant Women.

Additional resources for Public Health Officials, and State and Local Governments:

A copy of the CDC Interim Response Plan for how to deal with a local Zika outbreak.

Recommendations for Zika Vector control (CDC)

Additional resources for Individuals and Businesses:

How to protect against mosquito bites (2 page PDF from the CDC)

Additional resources for Doctors and Health Professionals:

Resources in multiple languages are available through the Centers for Disease Control and Prevention.

How Mosquitoes Bite: Get smart quick

Posted on June 22, 2016

Summer has arrived in Birmingham, and with it comes mosquito season. Given our research on Zika, and other mosquito-borne diseases, we would like to share some facts about how mosquitoes bite as part of our “Get Smart Quick” content series.

So, in 400 words, how do mosquitoes actually bite?

First, only female mosquitoes bite. They require the nutrients found in blood to produce eggs. Male mosquitoes feed mostly on flower nectar.

When feeding, the mosquito uses her proboscis — the long needle-like feature on her snout — to identify and extract blood from its target. However, this process is slightly more involved than most people think.

The proboscis (pro-boss-sis) is made up of six needles hidden under a protective sheath called a labium. When she bites, the labium folds backwards, exposing the six needles that make up her proboscis. These include:

A pair of maxillae, which have tiny saw-like teeth at their tips, used to pierce and cut the skin.

A pair of mandibles, inserted alongside the maxillae, used to spread the skin. The mandibles also provide leverage for digging the other needles deeper into the skin.

The Hypopharynx is a hollow needle used to secrete a saliva-like chemical that prevents blood from clotting. This saliva also causes the itchy reaction people experience, and serves as the fluid through which a female mosquito can transfer disease.

The labrum, the largest of the six needles, is a flexible straw-like feature used to explore for blood. Receptors at the tip of the labrum can detect naturally-occurring chemicals found in blood vessels, and guide the needle to its source. Like a modern oil or gas drill, the labrum can maneuver at sharp angles and explore horizontally underneath the skin surface (Check out this video captured by researchers at the Institut Pasteur in Paris). Once a vein is found, she uses the labrum to suck the blood.

While feeding, a mosquito will separate water from the blood and squeeze the water out of her rear end. This allows her to retain the greatest possible amount of nutrient-rich blood in each feeding.

The A. aegypti and A. albopictus will produce between 100-200 eggs per batch, and may lay approximately three batches in their 8-10 day lifecycle.

Eggs are often laid in, or near, standing water. However, A. aegypti eggs can survive in dry climates for periods longer than a year before hatching. Under these conditions, they hatch immediately after being submerged in any amount of water. Thus, the A. aegypti mosquito population is very difficult to control.

To learn more about how to protect yourself from A. aegypti and A. albopictus, visit the CDC page on Zika prevention.

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