Tag: Drug Discovery

New drug discovery collaboration targets novel treatments against diseases

Posted on September 20, 2017

Southern Research and the University of Tennessee Health Science Center (UTHSC) have formed a partnership to advance promising research that could lead to new drugs that address unmet medical needs.

The collaborative program links the drug discovery and development expertise of Birmingham-based Southern Research with UTHSC’s four-campus research network, which was involved in sponsored programs valued at $240.5 million in fiscal year 2016.

“We believe there are a lot of synergies between the two organizations,” said Mark Suto, Ph.D., vice president of Drug Discovery for Southern Research. “UTHSC brings novel scientific insights into diseases with poor treatment options, and we have proven capabilities in drug discovery and development.

“This collaboration with talented UTHSC researchers has great potential to lead to significant discoveries,” Suto added.

Southern Research HTS — Southern Research’s drug discovery efforts are aided by a High-Throughput Screening system.

The new UTHSC/SR Collaborative Research Network (CORNET) Award in Drug Discovery and Development represents an extension of a program launched by Steven R. Goodman, Ph.D., vice chancellor for research at UTHSC in 2016.

The CORNET Awards are designed to provide seed money to support new collaborative research teams and their projects. To-date, the program has provided over $1.1 million in funding to promising university research teams.

Glen E. Palmer, Ph.D., an associate professor in the College of Pharmacy at UTHSC, has been selected to receive the first jointly funded UTHSC/SR CORNET Award. Palmer is targeting the development of an entirely new class of antifungal medications to combat a range of invasive fungal infections, which are blamed in an estimated 1.5 million deaths a year.

“I want to congratulate Dr. Glen Palmer on being our first UTHSC/SR CORNET Award recipient and a second-time CORNET awardee,” Goodman said. “The UTHSC/SR CORNET Award is focused on drug discovery and development for any human disease. We are hopeful that Dr. Palmer’s exciting work and our partnership with Southern Research will lead to a new class of medications against invasive fungal infections.”

TEAMWORK APPROACH

Under the new program, UTHSC scientists can apply for funding to advance their research. The partnership is awarding Palmer $50,000 per year for up to two years, with funding for year two dependent upon progress made in year one.

Research projects receiving funding from the UTHSC/SR CORNET Award can take advantage of the shared resources of Southern Research and UTHSC to facilitate drug discovery and development efforts aimed at any disease.

Southern Research Suto — Mark Suto is vice president of Drug Discovery at Southern Research.

Southern Research’s established drug discovery infrastructure will play a key role in the partnership. The organization’s High-Throughput Screening (HTS) Center has a library of more than 1 million compounds and state-of-the-art robotic equipment for a wide variety of screens.

The Birmingham-based non-profit also has deep expertise in medicinal chemistry and pre-clinical drug development, along with bio-containment laboratories and other resources.

Southern Research scientists have discovered seven FDA-approved drugs used in cancer treatment and have evaluated a significant percentage of all medicines on the market.

Southern Research and UTHSC will jointly own intellectual property resulting from projects receiving support from the program. Outside partners will be sought for clinical development and commercialization when projects reach an advanced stage.

INITIAL PROJECT

Palmer’s research project, titled “Targeting the Aromatic Amino Acid Synthesis Pathway to Develop a New Class of Broad Spectrum Antimicrobial Agents,” aims to develop first-in-class broad-spectrum antimicrobial agents for the treatment of what are often fatal invasive fungal infections.

These infections are a serious and growing global health problem, with mortality rates often exceeding 50 percent for many fungal pathogens. Disturbingly, some of these pathogens are developing resistance to the antifungal drugs now in use.

Southern Research drug discovery — Researcher Glen Palmer of the University of Tennessee Health Science Center is targeting a new antifungal drug in the partnership with Southern Research.

“Mortality rates associated with invasive fungal infections have remained alarmingly high, as many of the antifungal drugs currently available are ineffective in treating these infections, or in some cases themselves are toxic to the patients,” Palmer said.

“Over the last few years, my lab has devised some novel approaches to discover new antimicrobial compounds. The collaborative effort between the University of Tennessee Health Science Center and Southern Research will provide a framework with the resources needed to apply these methods on a scale at which they can have a real impact,” he added.

“Additionally, it will bring the know-how and experience needed to progress the experimental therapeutics we discover towards new and improved drugs to ultimately improve the prognoses of patients with life-threatening invasive fungal infections.”

Southern Research’s HTS Center will assist Palmer in screening around 200,000 compounds for active chemical leads as part of the project. Southern Research’s Chemistry Department will play an integral role in the work after the initial active compounds are identified.

Researching radiosensitizers, a new class of drugs that would make tumors more vulnerable to radiation therapy

Posted on May 24, 2017

Two out of three cancer patients are treated with radiation, but the therapy often fails to wipe out the tumor or slow its growth. Southern Research is working to develop a new class of drugs that will help the radiation deliver a more powerful punch to the disease.

Dr. Bo Xu, M.D., Ph.D., Distinguished Fellow and Chair of Southern Research’s Oncology Department, said a radiosensitizer, as this kind of drug is known, would greatly benefit cancer patients by improving the success rate of radiation by reducing resistance to the treatment.

“Our project focuses on making those tumor cells more vulnerable to radiation by targeting a critical survival mechanism that allows them to recover from the effects of radiation,” Xu said.

It’s a challenging project, in the works for almost a decade. It got started when Southern Research scientists began looking at fundamental biology concepts to identify a pathway that could play a role in the ability of cancer cells to survive radiation.

Southern Research Bo Xu radiosensitizer — Southern Research’s Dr. Bo Xu is working to develop a radiosensitizer, a drug that would make tumors more vulnerable to radiation therapy.

They discovered that disrupting the tumor’s self-protection mechanism – in this case, an interaction between two specific proteins – makes the cancer more sensitive to radiation treatment, Xu said.

“The whole idea is to use this strategy to find a new drug that can be used by patients who receive radiation. This drug wouldn’t have toxicity because if it got into the cell it wouldn’t mess up the major functions of the protein network,” he said.

“It would only work when radiation is delivered, and that radiation would be more effective. It’s like a catalyst.”

Using funding from the Alabama Drug Discovery Alliance (ADDA), a partnership with the University of Alabama at Birmingham, Southern Research scientists recently scanned thousands of compounds to identify potential drug candidates. The focus now is to validate the results of those scans and to identify lead compounds for more testing.

“Our hope is that in three years, we can identify a novel class of radiosensitizers that can help the approximately two-thirds of cancer patients who will eventually receive radiotherapy,” Xu said.

CRITICAL INTERFERENCE

While some forms of cancer, such as lymphoma, are sensitive to radiation therapy, many others are not. Solid tumors with a low supply of oxygen, called hypoxic tumors, are tough to treat with radiation. So are cancer cells with a high DNA-repair capability.

To develop a radiosensitizer, Xu is taking aim at a protein that binds to DNA and recognizes the damage being done by radiation. The protein then joins forces with an enzyme to initiate a molecular repair job.

“If that recruitment is successful, then the DNA damage will be repaired, and the cancer cell will survive,” Xu said. “What we’re trying to do is to block this protein from finding the other one, so that the repair process will be diminished or affected. That way, the tumor cells will die.”

To prevent the DNA repair job from getting started, Xu is investigating a small peptide mimic, a small sequence of amino acids that is similar to a human protein but just a fraction of its size. These strands get to the site to block the interaction of the two natural, full-size proteins.

“This interference makes the cancer cell more vulnerable to radiation treatment,” he said.

Radiosensitizers are in demand, but they have proved difficult to develop. While the concept has been around for half a century, very few radiosensitizers have actually become available, according to Xu.

“While there are compounds that work synergistically with radiation, there are few drugs that were developed as a pure radiosensitizer,” he said.

In addition to the ADDA, the National Institutes of Health and the Department of Defense prostate cancer program have provided Southern Research with funding for this research over the years.

Southern Research joins Alabama bio-focused trade mission to Europe

Posted on April 20, 2017

Southern Research infectious disease researcher Tim Sellati, Ph.D., will join an Alabama delegation on a trade mission to Germany and Denmark next week that aims to raise the profile of the state’s bioscience sector and create pathways for collaboration.

Kicking off Monday, the “Alabama Life Sciences Trade and Investment Mission” features high-level networking events, expert briefings, presentations, and visits to biotechnology parks in Berlin and Copenhagen.

“Participating in Alabama’s European bio-focused trade mission provides Southern Research with an opportunity to showcase our organization’s extensive capabilities in life sciences while also sharing valuable information about the scope and vitality of the state’s biosciences sector,” said Art Tipton, Ph.D., president and CEO.

“As a group, the Alabama trade mission delegation can make connections and build relationships with counterparts in Germany and Denmark that can lead to productive research partnerships and strategic collaborations,” Tipton added.

Southern Research Europe trade mission — Infectious disease researcher Tim Sellati will share information about Southern Research’s life sciences capabilities on next week’s European trade mission.

Both Germany and Denmark have substantial life sciences industry concentrations. Germany is a leading international biotech hub and a primary location for pharmaceutical research and production. Denmark possesses an extensive research and development network and Europe’s largest commercial drug pipeline.

COMMUNICATING CAPABILITIES

Sellati, Distinguished Fellow and Chair of the Infectious Disease Department in Southern Research’s Drug Discovery Division, said he will share details about the Birmingham-based non-profit organization’s expertise in life sciences during presentations in both Berlin and Copenhagen.

“We obviously have a lot to be proud of in terms of our drug discovery and drug development capabilities,” Sellati said. “What I want to achieve by attending this mission is to communicate the diverse capabilities of Southern Research to groups in Europe.”

Sellati said Southern Research and Alabama’s emerging life sciences sector can benefit from collaborative opportunities and connections developed on the trip to the European bioscience hotbeds.

“The best science — whether it is basic research, translational research, drug discovery or drug development — simply cannot be done in a silo,” he said. “No one individual, no one institution has cornered the market on all the details necessary to move an idea from that light-bulb moment into a clinic so it can help a patient. It’s going to have to build upon a teamwork effort.”

In addition, interest in establishing broad international research partnerships is increasing within the scientific community as pressures build on government research funding, Sellati added.

“That’s really what is necessary to tackle some of the most significant public health challenges that we face, whether it be Ebola, Zika virus, Lyme disease, HIV/AIDS, or influenza,” he said.

“We know it is not a matter of if but when the world will face another influenza pandemic. We have no idea what Mother Nature has in store for us next month, next year, five years from now, in terms of infectious disease challenges.”

BIOTECH PARKS

Berlin biotech park — The Alabama trade mission delegation will visit Berlin Buch, one of the largest biotech parks in Germany.

While in Berlin, the Alabama delegation will visit BiotechPark Berlin-Buch, one of the largest such facilities in Germany, with more than 60 companies carrying out research, development and production. The team will also visit Bayer’s CoLaborator, an incubator for startups on the company’s campus.

In Denmark, there will be a tour of the Copenhagen BioScience Park (COBIS), a facility in the heart of the Medicon Valley bio-cluster that houses labs, startups and mid-size companies.

Greg Canfield, secretary of the Alabama Department of Commerce, is leading the life sciences trade mission, which begins in Berlin on Monday and concludes in Copenhagen on Friday.

The Alabama delegation includes two dozen representatives of bioscience organizations and companies, economic development specialists, elected leaders, and university officials.

Researcher Tim Sellati seeks genetic clues in Lyme disease mystery

Posted on April 13, 2017

Infectious disease researcher Tim Sellati, Ph.D., has spent much of his career trying to solve the central riddle of Lyme disease – why the tick-borne infection causes minor symptoms in some people but leaves others with lingering conditions such as arthritis and neurological problems.

“People should be very concerned about Lyme disease because we don’t have all the answers,” said Sellati, Distinguished Fellow and Chair of the Infectious Disease Department at Southern Research. “We don’t know who is going to develop symptoms and who is not, who is going to respond to treatment and who is not.

“If you are dealt a bad deck of genetic cards, you may suffer debilitating symptoms associated with this bacterial infection,” he said.

Sellati’s warning comes as tick activity begins to rise across the United States with the arrival of spring, triggering new cases of Lyme disease. The infection, caused by the bacterium Borrelia burgdorferi, is transmitted to humans through the bite of an infected blacklegged deer tick.

Lyme disease is the most common tick-borne illness in the U.S., according to the Centers for Disease Control and Prevention. Though the precise number is hard to pinpoint, the CDC estimates that 329,000 cases occur in the U.S. each year.

Most Lyme disease cases are concentrated in the Northeast and upper Midwest, but the illness is reported in many other states every year, including Alabama.

“This is not a deadly infectious disease, but it can take a person who is used to an active lifestyle and they can have symptoms that make it very difficult for them to even get out of bed in the morning,” Sellati said. “It truly impacts quality of life.”

LYME ARTHRITIS

Initial symptoms of Lyme disease include a rash shaped like a bull’s eye around the infected area, fatigue, headaches, and fever. In most cases, these symptoms can be successfully treated with antibiotics.

Untreated cases can result in more severe symptoms. In addition, some people develop what’s called Post-Treatment Lyme Disease Syndrome (PTLDS), which can be debilitating.

Serious symptoms include severe headaches, neck stiffness, nerve pain, short-term memory problems, irregular heart beat (Lyme carditis), facial paralysis, and inflammation of the brain and spinal cord.

As a graduate student at the State University of New York at Stony Brook on Long Island, New York, in the early 1990s, Sellati became keenly interested in another of these serious symptoms: Lyme arthritis.

“I wanted to understand why, if two individuals are infected with this bacterium that has the capacity to cause arthritis, some people develop the arthritis and some don’t.”

THE FIRST-RESPONDERS

Unraveling the mystery is a major thrust of his research today, which broadly focuses on the host-pathogen relationship in infectious diseases transmitted by ticks and mosquitoes.

In Lyme disease, this interaction begins with the body’s response to the invading bacteria – a defensive counterattack by cells in the bloodstream called neutrophils, which act as the innate immune system’s first-responders.

“These are the equivalent of Pac-Men — they run around in the bloodstream and try to gobble up bacteria and viruses that invade our body,” Sellati said. “When the bacteria that causes Lyme disease enters the joint, it triggers these neutrophils to migrate out of the bloodstream and into the joint tissue itself.

“They are supposed to kill and clear the bacteria. They’re usually very effective at doing so,” he added. “But for some people, this works better than for others. And this begins to provide insight into why some people develop very severe arthritis and others don’t.”

‘GENETIC BAGGAGE’

Southern Research Sellati Lyme disease — Infectious disease researcher Tim Sellati, standing, is seeking to understand why Lyme disease causes minor symptoms for some people while leaving others debilitated. He is being assisted by Shiva Kumar Goud Gadila.

Another puzzling aspect of Lyme Disease is why most individuals infected with the bacteria after a tick bite respond to antibiotics while others end up with serious symptoms despite treatment.

Sellati believes genetics plays a significant role in PTLDS, and he’s drilling down into the “genetic baggage” that these patients bring to the host-pathogen relationship for clues. This approach could lead to improved treatment options.

“If we can identify up-front those individuals with genetic markers suggesting that antibiotic treatment is not going to be sufficient, then we can investigate what else we can do to prevent the lifelong debilitating symptoms that they are genetically prone to develop,” he said.

To better understand how genetics influences the likelihood of developing Lyme arthritis, Sellati’s team at Southern Research has worked with different strains of mice, including those naturally susceptible to Lyme arthritis and those resistant to it.

“We used this mouse model to focus our attention on specific proteins that are displayed on the surfaces on those neutrophils and macrophages, another Pac Man-like cell in the bloodstream that runs around gobbling up bacteria and viruses to kill them,” Sellati said.

THE CD14 CLUE

The work helped the Southern Research team better understand the role of a gene called CD14 in the development of Lyme arthritis. CD14’s protein is a key player in the human innate immune system, the important first line of defense against infections.

“Now, the interesting question is that if you and I both have the infection, and you have very severe Lyme disease arthritis and I don’t, is that because you have less CD14 decorating the surface of your cells than I do?”

To get a definitive answer, it will be necessary to inspect individual cells for the absence of CD14’s protein. Sellati intends to do just that, using flow cytometry, a technology that suspends cells in a stream of fluid and passes them by an electronic detection apparatus.

Eventually, he would like to take a large-scale look at the genetics of the human population and those individuals who develop a very severe and persistent inflammatory response to the bacteria. These are the individuals who suffer from PTLDS.

“Is the reason these individuals fail to respond to antibiotic treatment because of a genetic defect in some of their innate immune responses that allow other individuals to rapidly, effectively clear and kill the bacteria?”

The answer to this intriguing question will inform the development of novel treatment options for those suffering with PTLDS.

Internship program offers research experience, attracts bright minds to science

Posted on January 27, 2017

College students from across the U.S. are getting firsthand experience with the innovative work conducted at Southern Research in the latest generation of the nonprofit’s internship program.

Interns from Princeton University, Emory University, the University of Virginia, Birmingham-Southern College, the University of Alabama, and the University of Alabama at Birmingham (UAB) are among those who have participated and gained experience similar to that found in potential future careers.

Southern Research internship — Daniel Unger, a UAB senior majoring in chemistry and neuroscience, is working with a Southern Research team to develop a small molecule target for anti-HIV drugs.

The internship program within each department at Southern Research (SR) offers different opportunities. In general, most students do research for course credits. During the summer months, SR has paid interns which allows the students to gain additional experience outside of the classroom.

Southern Research has had various internship programs, but the newest program was initiated by Corinne Augelli-Szafran, Ph.D., director of the Chemistry Department in the Drug Discovery division.

“The intern program at SR is an excellent opportunity for the students to get hands-on experience in a laboratory. In addition to having the students exposed to a drug discovery environment, this program contributes to the Chemistry Department while reaching out to the community,” she said. “This type of program is good for everyone involved.”

In the Chemistry Department, a team of more than 25 chemists works on various research programs, including those involving treatments for Lou Gehrig’s disease (amyotrophic lateral sclerosis), Parkinson’s disease, Alzheimer’s disease, tuberculosis, kidney disease, HIV, and a wide range of cancers. The department is responsible for the preparation of potential new chemicals that will become drugs.

INITIATING A PROGRAM

Augelli-Szafran’s career in drug discovery research spans 30 years, with stints at Harvard Medical School, Parke-Davis, and Pfizer. At both of the big pharma firms, there were internship programs that drew students from neighboring universities into the workplace. At Harvard, she initiated a student internship program similar to the one she initiated at Southern Research.

When she came to SR, there was no such program in place at the time. What resulted in the Chemistry Department, is a program where students can earn course credits. Throughout the term, the students work with a mentor and do a presentation or write a research report at the end of the term.

“It’s been over a year now since we started the program, and we’ve had seven students come through in Chemistry,” she said. “They work in the lab, they do chemistry reactions, they make compounds, isolate them, purify them and characterize them – the same things a chemist would do.”

During their time in the program, if students are able to make a few compounds to be tested, it’s a major accomplishment, Augelli-Szafran added.

“It’s a great experience to learn how to do the chemistry. It’s just great exposure, and it can sometimes help the students decide what to do after undergraduate studies, whether to pursue further education or seek a job in a certain specialty.”

LAB EXPERIENCE

For the Drug Development division, the nine interns who worked there last summer served a great need, said Sarah Ziegler, Ph.D., biosafety program and compliance manager.

The group mainly worked on biosafety issues – keeping workers safe and regulatory compliance – in the division that is focused on taking pharmaceuticals and equipment to market and all that entails. The Drug Development division is responsible for a wide range of testing activities.

Out of the nine interns, Southern Research hired three for full-time positions after their internships were over.

“It was a way for us to get in help, but they also had a great perspective in a more innovative way,” Ziegler said. “They were mostly focused on biosafety and working with us on inventorying samples. They also did paperwork for us and lab cleanup. It was not necessarily the most fascinating work, but it was definitely very helpful for us.”

For the interns, the experience offered real-world work experience in a lab setting, she said.

“They actually had a lab they were in charge of, so they were understanding how to function in that arena. Their projects spanned the whole Southside campus. They interacted with people from Drug Discovery and Drug Development, and they met researchers in every lab.”

Part of the program involved a weekly lunch and learn where Ziegler invited interns from across the campus to hear from Southern Research scientists and other professionals.

“We had people talk about quality, human resources, Zika, influenza and more. It was really interesting, and I even learned things about my organization I didn’t know,” Ziegler said.

EXPLORING CAREERS

Interns working in the Drug Discovery division say the experience they have gained is invaluable.

Birmingham-Southern College students Katie Russell and Abigail Holt are both interning at SR during the month of January to explore their future career and education paths.

Russell, a junior chemistry major, is learning organic synthesis techniques and how to analyze structure and purification data. She is an intern for postdoctoral researcher Shilpa Dutta, Ph.D., who is working on small molecule inhibitors for cancer therapeutics.

“I’m interested in the drug discovery career path, and I want to go to grad school,” Russell said. “I’ve done research work for one of my professors at Birmingham Southern, and I wanted to see how the process varies in an industry setting.”

Holt, a sophomore chemistry major, said she’s always been interested in pharmaceuticals and she’s trying to decide whether she wants to work as a researcher for a large firm.

“I think I’m really learning the most about day-to-day life and how professional chemists do their jobs instead of just being in a lab with a bunch of my classmates,” she said. “Even if I don’t end up becoming a researcher at a big pharmaceutical company, this internship has been really helpful in figuring out what I want to do. I’m glad I had the opportunity.”

UAB seniors Jaden Cowan and Daniel Unger are in the middle of longer internships. Cowan has been with Southern Research since last May, while Unger joined in August.

Cowan, a chemistry major, initially did the internship for school credit, and he liked it so much he signed up for another semester to do his senior thesis. The thesis is on the work he’s done so far, which is creating compounds that could be used in an anti-viral drug.

His ultimate goal is to become a research scientist. During his time at SR, he has set up experiments, monitored those, run tests on the compounds, and analyzed the results.

“Since I’ve been here, I’ve decided I’m going to try to obtain a Ph.D. in chemistry, and all these skills I’ve learned so far during this internship are going to be directly used in graduate school,” Cowan said. “This is good experience working in a professional lab alongside professional researchers. They’re prepping me so I can be independent and work in a lab by myself later on.”

Unger, a chemistry and neuroscience major, joined Southern Research after reconsidering his career plans.

“I added my chemistry major in the spring of last year, after I decided to look into career options other than medicine. I came the realization that I really enjoyed teaching,” he said. “So I decided to get a Ph.D. in chemistry, and I needed hands-on experience in the lab.”

Currently, Unger is working with a team on a project to develop a small molecule inhibitor as an anti-HIV therapy, a compound that essentially stops the virus from being able to replicate itself.

He sets up reactions on his own, as guided by his research mentor, and he follows the reactions, checking to see when they are completed. He also isolates and characterizes products from various reactions.

“It’s absolutely been beneficial, and I feel I’ve learned a lot. I have a much better grasp on what’s involved in doing the work as I prepare for grad school,” Unger said.

ATTRACTING TALENT

Dr. Bo Xu, MD, Ph.D., distinguished fellow and chair of the Oncology Department, said the internship program helps Southern Research attract more talented people to join the nonprofit.

Xu notes SR’s long and storied history when it comes to cancer research, which dates to the 1940s and includes more than $90 million in grant funding from the National Institutes of Health alone.

“It is part of our mission that we want to attract more talented people to join us, to be future scientists,” he said. “We want to see them get involved and engaged in the early stages of their career and training.”

Interns in the Oncology Department typically are assigned a small project, as well as a mentor who provides hands-on training. They’re taught how to design an experiment, analyze the data, write a report and present it to the entire department at the end of the term.

The subject matter the interns are studying is the cutting edge of cancer research, Xu said.

For example, this year a student from UVA shadowed a Southern Research scientist and learned about immunology/oncology research, specifically how to culture lymphocytes and how to design experiments for potential treatments.

“Basically we are having more young people come and learn and understand what science is, what cancer research is and how cancer research can help people,” he said.

Robert R. Meyer Foundation gift boosts Drug Discovery efforts

Posted on January 23, 2017

Birmingham’s Robert R. Meyer Foundation is supporting Southern Research’s Drug Discovery program with a $500,000 gift that aims to accelerate efforts to find new treatments for unmet medical conditions and rare and neglected diseases.

The contribution renews close ties between the Birmingham-based non-profit research organization and a charitable trust that became an important backer of its scientific work more than 60 years ago.

Southern Research has earned a solid reputation in drug discovery, with seven FDA-approved anticancer drugs, a number that ranks it among the most prolific in the field. In addition, Southern Research’s labs have screened many other potential medicines, and its researchers have developed a robust pipeline of promising therapeutics.

Southern Research Meyer Foundation — John Meyer, front row, second from right, stands for a photo at the dedication of Kettering-Meyer Lab II in 1958. His wife is next to him, and daughter Nancy behind him.

“The Robert R. Meyer Foundation’s longstanding support of Southern Research has been fruitful, contributing to many discoveries made by the organization’s scientists that have improved the lives of people battling cancer and other serious diseases,” said Beverly Baker, an Advisory Committee member for the foundation.

“The foundation’s leadership is confident that this gift will facilitate additional insights that lead the way to new treatments,” Baker added.

EARLY SUPPORT

The Meyer Foundation has supported Southern Research since 1953, when it provided $100,000 to match funding from the Charles F. Kettering Foundation for the construction of the Kettering-Meyer Laboratory. The Meyer Foundation made another significant contribution in 1957 to facilitate construction of a second Kettering-Meyer Lab.

In addition, the foundation has supported Southern Research’s cancer programs with other donations over the years.

“Significant gifts from the Robert R. Meyer Foundation in the 1950s enabled Southern Research to make important advances in drug discovery and have contributed to the impact our research and drugs have made on patients around the world,” said Art Tipton, Ph.D., president and CEO of Southern Research.

“The foundation’s latest gift will allow us to continue to explore important scientific breakthroughs that are high-risk, high-reward endeavors, rarely funded through government grants,” Tipton added. “This is the kind of research that results in the discovery of new drugs.”

Southern Research’s Drug Discovery division focuses on identifying novel treatments for serious conditions such as cancer, Parkinson’s disease, Alzheimer’s disease, diabetes, and viral and bacterial infections.

The division works as a partner of the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Institute of Drug Abuse, among others. It also collaborates with the Cystic Fibrosis Foundation, the Muscular Dystrophy Foundation, and other non-profit organizations and research institutions.

“Southern Research has the unparalleled capacity to investigate a wide range of potential treatments for complicated conditions,” said Mark J. Suto, Ph.D., vice president of the Drug Discovery division.

“Our innovative research programs and unique technological capabilities position the scientists at Southern Research to investigate possibilities and achieve meaningful outcomes.”

IMPORTANT CONTRIBUTIONS

The Robert R. Meyer Foundation was formed in 1942, just one year after the founding of Southern Research. Over the years, it has contributed more than $65 million to hundreds of charitable organizations.

Robert Meyer was a prosperous hotel operator with properties in Birmingham; Baltimore; Jacksonville, Florida; Nashville and Knoxville, Tennessee; and Raleigh, North Carolina. He served on the boards of the Waldorf Astoria and Governor Clinton hotels in New York City, as well as local enterprises such as DeBardeleben Coal and Woodward Iron.

He also served on Southern Research’s board of directors in 1946, one year before his death. His son, John Meyer, became a member of the board the next year, serving until 1970.

John Meyer was optimistic that cancer research would unravel the mysteries of the deadly disease and yield new treatments. At the dedication ceremony for the Kettering-Meyer lab on Dec. 17, 1953, John Meyer introduced his oldest daughter, Jane, to those attending the event.

“It seems particularly appropriate that youngsters of Janie’s age group should play a part here since their generation undoubtedly will be among the largest beneficiaries of current cancer research,” John Meyer said. “It is not only possible, but altogether probable, that by the time this young lady reaches maturity, the battle with cancer will have been won.”

While the struggle has not yet been won, the Meyer Foundation’s latest gift will help Southern Research continue the fight through the search for new medicines.

Drug discovery scientist Mark Suto named to National Academy of Inventors

Posted on December 13, 2016

Mark J. Suto, Ph.D., vice president of Drug Discovery at Southern Research, has been named a Fellow of the National Academy of Inventors (NAI) in recognition of his wide-ranging contributions to pharmaceutical research and drug discovery efforts.

During a career spanning more than 34 years, Suto has made significant advances in many clinical areas of the drug discovery process, including medicinal and computational chemistry, as well as lead optimization.

He holds 45 patents in the field of chemistry and drug discovery, along with numerous foreign equivalents. Suto’s patents focusing on ion channels in cells were acquired by pharmaceutical giant Pfizer. Several compounds from these patents are now in clinical trials.

“Throughout his career, Suto has fostered an international scientific reputation through high-impact publications, service as reviewer and editor for multiple prestigious scientific journals, 45 patents, and research presentations and lectures reflecting his broad expertise across the globe,” said Art Tipton, Ph.D., president and CEO of Southern Research.

CLASS OF 2016

Suto is the second NAI Fellow from Southern Research, joining Tipton, who was selected in 2013. Suto was among 175 leaders of academic invention named to NAI Fellow status today, according to an announcement.

NAI is a Tampa, Florida-based organization that recognizes inventors with patents issued from the U.S. Patent and Trademark Office and seeks to enhance the visibility of academic technology and innovation.

Each year, the NAI selects academic researchers who have demonstrated a spirit of innovation by creating inventions that lead to tangible improvements to quality of life and the welfare of society.

With the election of the 2016 class, there are now 757 NAI Fellows, representing 229 research universities and governmental and non-profit research institutes. The 2016 Fellows are named inventors on 5,437 issued U.S. patents, bringing the collective total held by all NAI Fellows to more than 26,000.

Suto and other new NAI Fellows will be inducted during a ceremony on April 6, 2017, at the John F. Kennedy Presidential Library and Museum in Boston.

“It is exciting to see the NAI Fellows Program continue to grow and honor the world’s most impactful academic inventors each year,” NAI President Paul R. Sanberg said in today’s announcement. “The 2016 Fellows exude innovative excellence and we feel truly privileged to welcome them to the Academy and recognize their remarkable contributions to discovery and invention.”

TARGETING THERAPIES

Suto joined Southern Research as vice president of Drug Discovery in 2011. At the Birmingham-based non-profit organization, he and his team focus on target identification and lead discovery and optimization of novel therapies for cancer, infectious diseases, and neurological diseases and disorders.

He serves as principal investigator on several NIH-funded programs, including the National Cancer Institute’s Chemical Biological Consortium, whose strategic mission is to accelerate the discovery and development of innovative cancer therapies.

Before joining Southern Research, Suto led major scientific and operational projects as an executive at pharmaceutical start-up companies. He also held positions of increasing responsibility in the chemistry department at Parke-Davis Pharmaceutical Research in Michigan.

Researchers find clue on how to block biofilm shields of bacterial infections

Posted on December 8, 2016

An investigation by Southern Research biologists reveals for the first time that fatty acids known as oxylipins play a critical role in the formation of the biofilm shield that protects disease-causing bacteria from antibiotics.

A paper explaining this process, “Oxylipins produced by Pseudomonas aeruginosa promote biofilm formation and virulence,” appeared Dec. 8 in Nature Communications, a peer-reviewed scientific journal. Authors are Javier Campos-Gomez, Ph.D., research biologist in Southern Research’s Drug Discovery Division, and Eriel Martinez, Ph.D., a researcher in the Campos-Gomez Laboratory.

Southern Research Campos-Gomez lab — Eriel Martinez, left, and Javier Campos-Gomez at work in the laboratory.

The findings have significant implications for understanding the formation of biofilms of bacterial pathogens with multiple antibiotic resistance mechanisms that are responsible for opportunistic infections in immunocompromised individuals and others, Campos-Gomez said.

“When the bacterium produces the oxylipins, the biofilm is stronger,” he said. “When you remove the capacity of the bacteria to produce oxylipin, it’s unable to make the biofilm, and the host organism is able to better fight off the infection.”

BACTERIAL COLONIES

Oxylipins are common in nature, and have been studied extensively in animals, plants, algae, and fungi, but the biological functions of these oxygenated fatty acids in bacteria have largely remained unexplained.

Campos-Gomez and Martinez studied P. aeruginosa – an antibiotic-resistant bacterium that causes disease in plants and animals – to better understand how oxylipins act to promote the organization of bacterial colonies into a more complex organization known as biofilm, where the bacteria are embedded inside a matrix that protect them from antibiotics.

Their findings show that oxylipin production essentially changes the bacteria from a free-swimming state to what amounts to a fixed state, allowing for the formation of a colony.

The researchers’ in vitro and in vivo (Drosophila flies) studies indicated that this step increased the ability of P. aeruginosa to form biofilms. They also demonstrated that the oxylipins produced by the bacterium promoted virulence in the flies and in lettuce leaves.

“We think oxylipins are signaling molecules that probably trigger other known or unknown pathways responsible for the biofilm production,” Campos-Gomez said.

PATHWAY FOR TREATMENTS

Oxylipin’s central role in promoting bacterial organization and biofilm formation may offer a promising opportunity for new medicines or therapies. The development of an oxylipin blocker could make a formerly antibiotic-resistant bacterial infection once again treatable, Campos-Gomez said.

As a next phase in their research, Campos-Gomez and Martinez plan to use Southern Research’s state-of-the-art high throughput screening facilities and large compound collection to identify agents that could act to block the production of oxylipin in bacteria.

In essence, understanding how bacteria rely on oxylipin production to create biofilms creates a new pathway for treatments that could save lives.

“It’s very difficult to treat these infections because of the biofilm, which acts as a shield against antibiotics and the host defenses, making it impossible for the infected host’s immune system to clear the bacteria from the body,” Campos-Gomez said.

“The host is unable to handle the infection, and it’s often fatal.”

Southern Research influenza program targets broad-spectrum antiviral against flu threats

Posted on December 7, 2016

Southern Research scientists are targeting a specific protein complex in influenza in the search for a new drug to counter a virus that infects more than 3 million people each year and has a history of catastrophic pandemics.

“Influenza remains a big killer,” said Mohammad F. Saeed, Ph.D., a research scientist in Drug Discovery who is directing Southern Research’s program to develop a treatment against the virus.

Southern Research influenza — Southern Research scientists are seeking to develop a drug that’s effective against several influenza strains.

Influenza is blamed in the deaths of between 250,000 and 500,000 people across the globe each year, according to the World Health Organization. In the U.S., annual flu deaths range from around 3,000 to just under 50,000, the Centers for Disease Control and Prevention (CDC) estimates.

Vaccines offer protection against seasonal influenza, but Saeed says there are many reasons to pursue the development of a broad-spectrum antiviral that’s effective against several strains of the virus. That’s the goal of his work, which is funded through a National Institutes of Health grant.

“Let’s say we have a pandemic like we had in 2009 with swine flu — the vaccine wouldn’t work against that because that is a different variety of influenza,” Saeed said. “Every now and then, you see a different strain of influenza entering human population and becoming more prevalent globally because the existing vaccines are ineffective against the new strain. To generate a vaccine for the new variety, it would take six to nine months, or a year.”

Scientists say the 2009 swine flu was a new form of the H1N1 influenza virus that rapidly spread around the globe much like the 1918 pandemic that killed as many as 100 million people, most of them young, healthy adults. The CDC put the death toll from the 2009 swine flu pandemic at 284,000 worldwide.

BIRD FLU DANGERS

In addition, the threat posed by avian influenza underscores the need to develop an effective antiviral treatment as a protective measure, Saeed said.

While bird flu doesn’t typically infect humans, there are no vaccines for these influenza strains. Plus, the H5N1 avian influenza virus has shown a very high mortality rate in cases of human transmission.

“Normally these viruses don’t jump species, from birds to humans, but our biggest concern is what if they acquire mutations in nature so that they can more frequently infect humans?” Saeed said. “That would become a big problem, because these viruses are more pathogenic than the influenza virus we see in human populations.”

With no vaccine available, a highly pathogenic mutated avian influenza virus would likely kill people in greater numbers, and even those otherwise healthy individuals who usually can fight off infection with the seasonal influenza viruses.

“That’s our concern, and that’s why we want to have drugs against influenza viruses,” Saeed said. “In an outbreak, if we don’t have time to get a vaccine in place, we’ll at least have drugs for people who are already infected to save their lives.”

TARGET: POLYMERASE

Researchers have developed drugs that are useful against influenza, but the virus can develop resistance.

For example, amantadine, which disrupts the virus release from infected cells in Type A influenza, and thereby prevents its spread, is no longer recommended for treatment of influenza in the U.S. because of resistance, Saeed said. The CDC says sporadic resistance has been spotted with oseltamivir, the most widely used antiviral flu medication.

“These viruses mutate all the time. That’s the way they work,” Saeed said. “For us, the important point is to target some protein in the virus that doesn’t mutate as frequently.”

The Southern Research team is targeting a protein complex in influenza viruses called polymerase, which plays a central role in viral replication. In recent years, scientists have made breakthroughs in revealing the structure of this protein complex, opening opportunities for sophisticated drug design techniques.

Additionally, the polymerase protein complex is relatively consistent across several influenza virus subtypes, meaning a drug that works against one form of the flu could work against many others.

“Without those proteins, the virus cannot replicate,” Saeed said. “If we can inhibit those proteins, we can stop the virus in its tracks.”

Scientists also believe that because this set of three proteins performs such an essential function to the virus, mutations within the complex should be rare. That means the likelihood of the virus developing resistance to a polymerase-targeted drug should be low.

DRUG DISCOVERY

Southern Research, whose antiviral work started in the 1950s, is well positioned to make advances against influenza.

High Throughput Screening on Zika — Scientist working with assays in Southern Research’s High Throughput Screening lab.

Scientists at the organization’s infectious disease labs in Birmingham and Frederick, Maryland, have studied a wide range of viral threats, from polio and HIV/AIDS to dengue and Zika. It has a vast library of compounds to examine for activity against influenza, and a state-of-the-art high throughput screening facility with dedicated experts to perform that operation at scale.

“We have a compound collect with approximately 500,000 samples available for screening against influenza viruses,” Saeed said. “We start with the seasonal and pandemic strains. Then we’ll test the compounds that show activity against the avian viruses.”

So far, the Southern Research team has tested about 200,000 compounds in the collection, turning up close to 900 “hits,” or agents that showed activity against influenza, Saeed said. Further screening determines whether the agents are acting against the targeted protein complex.

As part of the drug discovery process, Southern Research chemists assist by designing new molecules from the active agents that are better tolerated in the human body and consistently reach the target area in the virus.

“There are multiple subtypes of influenza viruses, so our goal in this program is to find small-molecule drugs that could potentially have activity against many different subtypes,” Saeed said.

“Influenza pandemics have killed millions of people, and in the case of an outbreak of a highly pathogenic influenza virus, there just won’t be time to develop a vaccine,” he added. “We need a drug against this threat.”

NIH orders High Throughput Screening for Zika

Posted on November 7, 2016

In 2014, Southern Research received funding from the National Institute of Allergies and Infectious Diseases (NIAID) through a multi-center U19 grant (U19AI109680) administered by the University of Alabama at Birmingham to conduct high throughput screening (HTS) against six disease-causing viruses: dengue, West Nile, SARS, influenza, Venezuela equine encephalitis complex, and chikungunya. With the program in place, and as Southern Research has completed screening the viruses, the National Institutes of Health (NIH) issued a supplementary $650,000 award for the Birmingham-organization to expand its program to include high throughput screening for Zika.

“Southern Research has a long history in antiviral research, including screening viruses in the same flavivirus genus as Zika, so we’re pleased the NIH saw fit to expand the U19 program to include screening on Zika,” said Bob Bostwick, Ph.D., director of the High-Throughput Screening Center at Southern Research. “For drug discovery purposes, we hope to identify compounds that work well across this entire genus.”

According to the supplemental grant, Southern Research will construct an assay for Zika that can be conducted in HTS, and test over 300,000 compounds against the virus, a process that will take nine months.

Developing robust screening capabilities

For Southern Research, compound screening has been a part of the organization’s efforts since the mid-1950s, when researchers began manually screening anticancer drugs under a contract with the National Cancer Institute (NCI). Around this same period, the Virus Research Division began evaluating antiviral agents against a wide range of pathogenic viruses, including the herpesviruses, poxviruses, acute upper respiratory disease viruses, and mosquito-borne viruses, such as Yellow Fever virus.

By the 1960s, the early work had already shown promise. Manual screenings conducted by the viral research team had identified the compounds that led to the discovery of Ara-A, an antiviral used to treat human herpesviruses, chicken pox, shingles, human cytomegalovirus — a cause of childhood hearing loss — and a lethal encephalitis.

In the 1980s, following the emergence of the AIDS epidemic in the United States, Southern Research expanded into HIV antiviral research through a series of contracts and grants with the United States Army and the NIH. This effort involved screening compound collections consisting of approximately 20,000 samples, and developing a staff of scientists proficient in working with many infectious diseases. By the following decade, the organization’s anti-HIV screening program had become the largest in the country.

While earning a global reputation for producing high quality antiviral research, Southern Research’s screening capabilities were expanding far beyond antivirals to include screening of other infectious diseases and cancer. In the late 1990s, the organization invested in emerging HTS technologies to maintain a prominent role at the forefront of drug discovery. This involved assembling a large compound collection — consisting of over 1 million samples — and acquiring robotic platforms for automated screening, thus enabling the organization to test hundreds of thousands of compounds for each new target. Eventually, the program would become involved in the NIH Roadmap Molecular Libraries initiative, and serve as one of twelve centers in the NCI Chemical Biology Consortium.

“Southern Research’s in-house screening capabilities are unmatched by most universities and private research organizations across the globe,” said Art Tipton, Ph.D., president and CEO of Southern Research. “With our Biosafety Level 3 (BSL3) facility, an active in-house library of over one million compounds, and a wealth of institutional knowledge, our researchers pride themselves on finding chemical structures needed to develop drugs against some of the greatest global health threats.”

High Throughput Screening and drug discovery

Today, HTS is an automated process that allows researchers to rapidly test a large number of compounds in order to determine their potential use as starting points for the invention of new drugs. With time and advances in technology, the process of screening compounds has evolved significantly from the early days. However, despite these advances, some things remain the same.

“Whether you are working on an antiviral or an anti-cancer medication, the drug discovery process is incredibly complex and often starts with screening,” said Bostwick. “HTS usually requires screening hundreds of thousands of compounds to find three or four good chemical starting points for medicinal chemistry.”

With the recent expansion of its U19 program to include screening of the Zika virus, Southern Research maintains a prominent global position in antiviral research. Its work has led to the fight against HIV/AIDS — supporting the United States government and numerous drug companies in the production of many of the FDA-approved antiviral drugs currently on the market — and screening of compounds that allowed for numerous other drug breakthroughs, including several against previously drug resistant strains of tuberculosis and malaria. Yet, despite this record of success, researchers admit a cure for Zika will still take time.

“Even though we know a lot about flaviviruses, discovering and developing effective therapeutic agents may take several years,” Bostwick continued. “Just like any other project we’ve undertaken, we will use data as our guide and hope our efforts will yield results which can be helpful to the scientific community.”

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Tag: Drug Discovery

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Developing robust screening capabilities

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