Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960)

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Hugh Alexander Brown

1960–2017

BIRTH 2 DEC 1960

DEATH 25 JULY 2017 • Franklin, Williamson County, Tennessee, United States of America

https://www.ancestry.com/family-tree/person/tree/176620477/person/412295825060/facts?_phsrc=llt1716&_phstart=successSource

https://www.asbmb.org/asbmb-today/people/090117/h-alex-brown-1960-2017

HE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY

2017-09-01-american-society-for-biochemistry-and-molecular-biology-h-alexbrown-1960-2017.pdf

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H. Alex Brown (1960 – 2017)

By Craig W. Lindsley and Lawrence J. Marnett

Sept. 1, 2017

The scientific community suffered a great loss on July 25, when H. Alex Brown passed away at the age of 56 after a long battle with an aggressive cancer. True to everything that Alex was, he retained his focus on science, his love and pride in his family, and an incredibly positive outlook throughout his treatment.

Alex Brown was featured in a 2003 Vanderbilt Reporter story on the founding of the lipid metabolites and pathways strategy consortium, known as Lipid MAPS.

PHOTO COURTESY OF VANDERBILT UNIVERSITY

The Bixler–Johnson–Mayes professor in the department of pharmacology and interim director of the Vanderbilt Institute of Chemical Biology at Vanderbilt University School of Medicine, Alex was an exceptional scientist, colleague and mentor. He was a leader in the field of lipidomics, the application of analytical chemistry, mass spectrometry and systems biology to lipid profiling in cells and tissues. He helped define the role that the enzyme phospholipase D, known as PLD, plays in intracellular lipid signaling pathways involved in growth promotion, invasive cancers, viral infection and immunology. Beyond his scientific prowess, Alex forged translational collaborations across disciplines and was a champion for quantitative science.

Alex grew up on the east coast of Florida close to the Kennedy Space Center. He attended Wake Forest University and received his Bachelor of Science with highest honors from Florida Institute of Technology and a master’s degree from Syracuse University. Alex received his Ph.D. in 1992 from the University of North Carolina at Chapel Hill working in the laboratory of T. Kendall Harden, where his lifelong interest in the complexities of cell signaling was born. He then pursued postdoctoral training in the department of pharmacology at the University of Texas Southwestern Medical Center with Paul Sternweis.

In 1996, Alex joined the faculty at Cornell University with appointments in pharmacology and biochemistry and molecular and cell biology. There, in 1997, he received the Sidney Kimmel Foundation for Cancer Research Scholar Award. While at Cornell, Alex used electrospray ionization mass spectrometry to develop the field of computational lipidomics in collaboration with Fred McLafferty. Al Gilman, then the director of the Alliance for Cellular Signaling, invited Alex to use this emerging technology to contribute to the AfCS research program.

In 2002, Alex was recruited to Vanderbilt University School of Medicine as the Ingram professor of cancer research in pharmacology, where he served as the director of the glycerophospholipid core for the lipid metabolites and pathways strategy consortium, known as Lipid MAPS, beginning in 2003. Since 2016, Alex had served as interim director of the Vanderbilt Institute of Chemical Biology, known as the VICB, which supports, through research and education, the application of chemical technologies to important biological problems. He was one of the VICB’s first recruits and previously a member of the executive committee. At the time of his passing, Alex was in the midst of executing a grand vision for the VICB that would have united chemistry and biology practitioners in translational endeavors. Alex trained nine Ph.D. students and supervised 13 postdoctoral associates while publishing more than 150 peer-reviewed research articles. He was generous with his time in helping others and in providing service to the research community. He served on editorial boards and publication committees for numerous journals, was an associate editor of the journal Molecular Pharmacology, and organized international conferences on lipid metabolism and signaling. He also served on the editorial board for the Journal of Biological Chemistry and the American Society for Biochemistry and Molecular Biology publications committee.

I, Craig Lindsley, first met Alex when I interviewed for a faculty position in the pharmacology department at Vanderbilt in 2006. I was immediately impressed by Alex’s passion for science and his drive to better understand the diverse roles of his beloved lipid signaling enzyme, PLD. After joining the faculty, I had my first of many lunch meetings with Alex, at which he asked if I thought we could develop selective ligands for the two isoforms of PLD, PLD1 and PLD2. That simple question sparked a 10-year collaboration between our labs that resulted in highly selective, allosteric PLD1, PLD2 and dual PLD1/2 inhibitors that enabled Alex to define the roles of the individual isoforms in oncology and infectious disease. Ten years, more than 2,000 compounds synthesized and assayed, and over a dozen manuscripts later, these small-molecule probes revitalized and revolutionized a stagnant field — held captive by a lack of chemical probes to prosecute — with what is now a high-profile target for drug discovery efforts. Throughout, Alex was an exacting scientist with an unwavering eye toward quantitation. The unmasking of the therapeutic promise of PLD is solely due to his pioneering efforts and vision, and if he had been given more time, there is no limit to what he would have accomplished.

I, Larry Marnett, had the pleasure of collaborating with Alex for most of his time at Vanderbilt. We used his lipidomic methodologies to characterize the mobilization and re-esterification of saturated and polyunsaturated fatty acids in the phospholipid pools of macrophages stimulated with inflammatory mediators. Simultaneously monitoring all the fatty acids moving around in all the phospholipids was amazing to me and analogous to removing the curtains from a mysterious world. We published nine papers from our collaboration; the last one appeared June 14 of this year. We had many conversations during and after his recruitment to Vanderbilt. They were always intense and never superficial; Alex valued details. The conversation that really stands out took place about a year ago. Alex had been working hard to regain funding after the support from various consortium grants had run out. He had written many grant applications on the role of PLD in infection and its potential as a target for antibiotic drug discovery. Over lunch, he said it was frustrating to have grants rejected when there was so much research to do but that he was not discouraged. The experience had forced him to look deeply at his results and priorities, which convinced him that he was not only headed in the right direction but was doing the most important work of his career. He said he felt energized, and not long thereafter he obtained an R01 to reboot his PLD program. Alex had a mental toughness and passion for science that few of our contemporaries display.

Alex’s long-time friend and colleague Stephen Traynelis of Emory University recalls Alex during his graduate and postdoc years. “I consider it an honor and privilege to have known Alex, who enriched the lives of virtually everyone he interacted with,” Traynelis said. “I will always remember the many deep conversations we shared about all aspects of science and life, his unwavering commitment to faith and family, and his impressive work to understand lipid biology. I remember asking Alex late in his postdoctoral fellowship what he planned to do, before he moved to Cornell. Alex replied, ‘I feel like the lipid membrane is perhaps the most poorly understood feature of cells yet the most dynamic. I plan to use the various skills I have learned to take apart the membrane, know all if its components and study its capacity for signaling. I think it will be transformational.’ And he did just that.”

Ken Harden was Alex’s Ph.D. adviser at UNC. “This is such a loss for science and for lipid signaling research in particular,” Harden said. “Alex was a uniquely talented and dedicated scientist — and, oh, how we will miss his robust voice, hearty laugh and wonderful sense of humor.”

Alex Brown with his daughter, Lindsey, his wife, Renee, and his son, Kyle.

PHOTO COURTESY OF RENEE BROWN

In the past few years, Alex’s research program turned toward infectious diseases, and he collaborated with Paul Thomas at St. Jude Children’s Research Hospital to uncover a novel role for PLD in influenza and other viruses. “Alex was a thorough and creative scientist who was able to see a problem from many angles,” Thomas said. “I was always excited to get a phone call from him, as it meant he had a new idea or new data to share about a project we were working on together. Most importantly, he was a good man who considered mentoring and the integrity of his work as his primary objectives.”

Paul Sternweis, Alex’s postdoctoral adviser at UT Southwestern, summed up what so many feel. “Alex was one of the best!” he said. “As a postdoctoral fellow in my research group, his creativity, unbounded energy, productivity and cooperativity made him a driving force for the whole group. It was a pleasure to see his willingness to vigorously take on daunting problems move him to the forefront of research fields and feed a thriving career. But more than this, Alex was a friend who brought much joy to those around him, including myself. He is truly missed.”

In addition to a research community that mourns his passing, Alex leaves behind his wife, Renee Brown, program chair of the School of Physical Therapy at Belmont University; his son, Kyle, a chemistry graduate student at the University of Wisconsin; and his daughter, Lindsey, an architecture student at Syracuse University.

While his serious demeanor was legendary, outside the lab, Alex was quite possibly the kindest, most generous and family-focused man many of us have ever known. And here is a little-known fact: It took many, many $1 Evan Williams shots at a Keystone meeting to witness it, but Alex had an uncanny ability to impersonate Eddie Murphy. As the whiskey flowed, Alex was transformed, and a large group was privy to a revival of “Saturday Night Live” circa 1979–1982. It was a thing of beauty and completely unexpected.

Rest well — you are dearly missed.

https://news.vumc.org/2017/07/26/vanderbilt-mourns-loss-of-pharmacologist-h-alex-brown/

Vanderbilt mourns loss of pharmacologist H. Alex Brown

Jul. 26, 2017, 2:04 PM

H. Alex Brown, Ph.D., the Bixler-Johnson-Mayes Professor in the Department of Pharmacology at Vanderbilt University School of Medicine, died from cancer Tuesday, July 25, at his home. He was 56.

H. Alex Brown, Ph.D.

Dr. Brown was a leader in the field of lipidomics, the application of analytical chemistry, mass spectrometry and systems biology to lipid profiling in cells and tissues. He helped define the role that the enzyme phospholipase D plays in intracellular lipid signaling pathways involved in growth promotion and invasive cancers.

For the past year, Dr. Brown served as interim director of the Vanderbilt Institute of Chemical Biology (VICB), which supports, through research and education, the application of chemical technologies to important biological problems.

“Alex was one of the first recruits to the VICB and was an active member of the executive committee before becoming director,” said VICB co-founder and former director Lawrence Marnett, Ph.D., who was appointed dean of Basic Sciences in the School of Medicine last year.

“He was a talented and rigorous scientist who was one of the best collaborators I’ve ever had the privilege of working with,” Marnett said. “Most importantly, he was a great friend to many at Vanderbilt and we will miss him terribly.”

Dr. Brown received his Bachelor of Science degree with highest honors from Florida Institute of Technology, a Master’s Degree from Syracuse University and his Ph.D. degree from the University of North Carolina at Chapel Hill in 1992.

At UNC he worked in the laboratory of T. Kendall Harden, Ph.D., in the Department of Pharmacology, where his lifelong interest in the complexities of cell signaling was born.

Dr. Brown pursued postdoctoral studies in Pharmacology at the University of Texas-Southwestern Medical Center with Paul Sternweis, Ph.D., and in 1996, joined the faculty of Cornell University with appointments in Pharmacology and Biochemistry, Molecular & Cell Biology.

It was at Cornell that Dr. Brown developed the field of computational lipidomics, which he then brought to Vanderbilt upon his appointment as professor of Pharmacology and Ingram Professor of Cancer Research in 2002.

Dr. Brown’s research program at Vanderbilt flourished. He established many research collaborations applying his lipidomic technology to the characterization of signaling pathways in various diseases including glioblastoma and non-alcoholic steatohepatitis.

He was a major contributor to multi-omic analysis of cell signaling through his participation in two “glue grants” sponsored by the National Institute of General Medical Sciences — the Alliance for Cellular Signaling and Lipid Maps.

In addition to his pioneering work on lipidomics, Dr. Brown maintained a long-term fascination with the role of phospholipase D in cell signaling.

He established a powerful collaboration with Craig Lindsley, Ph.D., a leader of Vanderbilt’s groundbreaking drug discovery program, which resulted in development of isoform-specific PLD1 and PLD2 inhibitors that have been widely used as probes and drug candidates.

Dr. Brown was a passionate and exacting scientist and mentor. He trained nine Ph.D. students and supervised 13 postdoctoral associates. He published more than 150 peer-reviewed research articles, served on the editorial boards and publication committees for numerous journals and organized multiple international conferences on lipid metabolism and signaling.

His contributions include serving as editor of a three-volume series on lipidomics and bioactive lipids for Methods in Enzymology and as co-editor with Dr. Marnett of a thematic issue on lipid biochemistry for Chemical Reviews in 2011.

Dr. Brown’s honors included the Sidney Kimmel Foundation for Cancer Research Scholar award in 1997 and in 2010 the Vanderbilt-Ingram Cancer Center High Impact Publications Award. In 2011 he and Dr. Lindsley received a Vanderbilt University Medical Center Academic Enterprise Faculty Award for Leadership of a Multi-Investigator Team.

Dr. Brown is survived by his wife, Renee Brown, Ph.D., program chair of the School of Physical Therapy at Belmont University, his son, Kyle, a chemistry graduate student at the University of Wisconsin, and his daughter, Lindsey, an architecture student at Syracuse University.

A memorial service for Dr. Brown will be held on Friday, July 28, at 4 p.m. at Saint Andrew Lutheran Church, 908 Murfreesboro Road, Franklin, Tennessee. Visitation will be at 3 p.m.

Vanderbilt mourns loss of former Bariatric Surgery director Clements

2016 (February 22 issue) - Chemical & Engineering News : "Gearing Up To Fight Zika : Researchers scramble to develop tools and treatments to combat the mosquito-borne virus"

Bethany Halford / C&EN Boston / C&EN, 2016, 94 (8), pp 33–36February 22, 2016 / Source (this was paid content) - [HP00AH][GDrive]

NOTE - Article also here : [HP0077][GDrive]

Mentioned : Dr. Thomas Patrick Monath (born 1940) / Sina A Bavari (born 1959) / NewLink Genetics Corporation / Zika virus epidemic (2015-2016) / Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960) /

[HP00AI][GDrive]

When the Pan American Health Organization put out an alert last May about the first confirmed cases of Zika virus infection in Brazil, the news barely registered. After all, compared with other mosquito-borne viruses, such as potentially life-threatening dengue and yellow fever, Zika seemed pretty harmless. Only 20% of people infected with Zika even become ill, and their symptoms tend to be mild—fever, rash, joint pain, and conjunctivitis.

But in January, nine months after the organization raised the alarm, doctors in Brazil reported a disturbing trend that coincided with Zika’s spread across the country. Since October 2015, more than 4,000 babies in Brazil had been born with abnormally small heads and brains—a rare condition known as microcephaly. Although further analysis lowered that figure by 462 cases, the sharp rise nonetheless has experts worried that Zika could be to blame. For comparison, Brazil reported just 147 cases of microcephaly in 2014.

Zika is also being blamed for an uptick in cases of Guillain-Barré syndrome, a potentially life-threatening disorder in which the body’s immune system attacks the central nervous system and causes paralysis. As with microcephaly, the evidence connecting Zika and Guillain-Barré is still circumstantial. Nevertheless, the link is strong enough for the World Health Organization to declare the Zika outbreak a public health emergency of international concern.

Margaret Chan, WHO’s director-general, said earlier this month that the virus is “spreading explosively” through the Americas, with cases of active virus transmission in at least 26 countries and territories in the Americas. Panic over the virus has prompted health officials in some countries to take the drastic measure of advising women to delay pregnancy for months or longer. In El Salvador, Deputy Health Minister Eduardo Espinoza asked women to avoid becoming pregnant until 2018.

With Zika making headlines for the past month, scientists have been scrambling to get a handle on the virus. Industry, government, and academic scientists have all announced efforts to develop and test treatments and vaccines. But the path ahead for these researchers is long and full of pitfalls. Even though Zika has been around for almost 70 years, surprisingly little is known about the virus and its basic biology. A PubMed search for “Zika virus” turns up mostly case studies.

What we do know is that Zika is a flavivirus, a member of the same family as dengue, yellow fever, and West Nile virus. Zika is primarily transmitted via bites from infected mosquitoes, but in recent weeks doctors have reported that the virus can be sexually transmitted as well.

It was first identified in a monkey in Uganda’s Zika forest in 1947, but only a handful of human Zika cases were reported until a 2007 outbreak in Micronesia’s Yap Island. An outbreak in French Polynesia followed six years later. Last November officials in that country reexamined the cases of microcephaly that followed the outbreak. Before the outbreak, about one case of microcephaly was reported each year. In 2014–15, officials found 17 cases of fetuses and infants with “central nervous system malformations,” which includes microcephaly.

As the case connecting Zika to serious health effects builds, the world would love a vaccine or treatment for the virus. But because so few have studied Zika, drug developers currently have few tools to work with. For example, there’s no commercially available, U.S. Food & Drug Administration-approved test to screen for Zika virus.

Tracking Zika in people is hard because it’s difficult to determine that they’re infected with Zika and not a related flavivirus or that they’re not infected with more than one virus, says Priscilla L. Yang, a flavivirus expert at Harvard Medical School. Simultaneous infection with Zika and another virus could cause health effects that haven’t been seen before.

Scientists can use polymerase-chain-reaction-based methods to distinguish Zika from other flaviviruses. But those tests are accurate only during the short window patients still have the virus in their system—about seven days after infection. By the time a patient has symptoms that warrant a visit to the doctor, the virus is no longer circulating in their bloodstream, Yang notes.

Another option is to look for antibodies against the virus. But Zika and dengue are closely enough related that antibodies to Zika also recognize dengue and vice versa. Making a definitive diagnosis based on antibodies is possible but becomes time-consuming and laborious, Yang says.

For scientists who have compounds that might be effective against Zika, actually testing them has been tough. “We have small molecules that seem to be broadly acting against dengue and West Nile virus,” Yang says. “We want to test them, but getting access to the live virus has been hard.” She’s heard that certain labs known to have the Zika virus have been bombarded with hundreds of requests from researchers.

Even if someone manages to access the live virus and can find a compound that kills it in cells, the researcher will hit another roadblock: To date, no one has published practical animal models of Zika virus to screen potential therapies against. Yang points to a paper from the 1970s in which scientists did an intracranial injection of Zika virus in newborn mice, but she notes that is a poor model because many small molecules can’t slip past the blood-brain barrier.

“We’re basically starting from scratch on this one, unfortunately,” says [Sina A Bavari (born 1959)], chief scientific officer (CSO) at the U.S. Army Medical Research Institute of Infectious Diseases. Bavari and colleagues are currently working with pharma companies to see if they have any compounds that inhibit Zika replication in cells.

They’re primarily interested in compounds that have passed the hurdles of Phase I or Phase II clinical trials but are sitting idle for business reasons. That’s because it can take upward of a year and a half just to get a new compound ready for Phase I. “My worry is that by the time we get something out the door, this outbreak will have already burned out,” Bavari says.

Scientists are also grappling with this question: If only 80% of people infected with Zika have symptoms, who would get the treatment? The most vulnerable patients are pregnant women, but Bavari points out, there’s a high bar when it comes to approving a medication that can be given to them. “They don’t even want to drink caffeine,” he says.

Other scientists are working to develop a vaccine against the Zika virus. Earlier this month President Barack Obama said he would ask Congress for $1.8 billion to combat Zika at home and abroad. Of those funds, $200 million would be used for vaccine development. The U.S. National Institute of Allergy & Infectious Diseases, Sanofi Pasteur, and NewLink Genetics are among the heavy hitters in the vaccine field who’ve said they’ll step up to the plate.

Even so, it could take three to five years before a vaccine is ready, experts say. [Dr. Thomas Patrick Monath (born 1940)], CSO of [NewLink Genetics Corporation]’s infectious disease division, led that firm’s efforts to develop an Ebola vaccine and was CSO at Acambis, where he worked on vaccines for dengue and yellow fever. Monath tells C&EN he thinks a large field trial of 10,000 to 20,000 people across multiple sites will be necessary to determine efficacy once a Zika vaccine is developed. “Only after those trials would you contemplate doing studies in pregnant women,” he says.

Monath also says because so many people who are infected with Zika never show any symptoms, it is more difficult to determine whether the vaccine has actually prevented infections. Still, he thinks a large enough trial should be conclusive.

But some scientists say the emphasis on vaccines is misplaced. “We just don’t know enough about Zika virus right now to run around and vaccinate people,” Bavari says. “Understanding the immunopathology and immunology behind it would be really prudent before starting a full vaccination program.”

Harvard’s Yang says developing a vaccine for every emerging virus is impractical. “Vaccines are, for the most part, specific. You have one virus, and you have one vaccine for it,” she explains. “I don’t think we’ll ever have the luxury of enough resources to get a vaccine against every single possible emerging virus or enough time to do it in a reactive way.”

One area that’s not getting as much attention, she says, is development of broadly acting antivirals that could keep a virus in check while the immune system fights it off. Classical antivirals go after a single viral enzyme, but viruses are quick to develop resistance to them. “If people could identify targets that have the potential to be effective against multiple viral pathogens, it could be game-changing,” Yang says.

[Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960)], a Vanderbilt University professor who works on antivirals, agrees. “There are so many viruses out there. We need to be working on a much more broad-spectrum approach to infectious disease,” he says. “If we can develop more tools to combat broad categories of viruses, I think we would be much better off than we are today.” [ Note - [Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960) passed July 25, 2017 ]

In the meantime, scientists agree that the research community needs to be more organized if it’s going to have a real shot at combating Zika. Yang thinks the first steps should be figuring out how to get the necessary reagents to the labs that need them and agreeing on standards so they can compare results and learn from each other’s work. “If you actually want to have some sort of impact, we all need to work together,” she says. In an encouraging sign, earlier this month, major scientific institutions and top research journals agreed to share data relevant to Zika virus.

Bavari agrees scientists need to be better at organizing their efforts, but he has doubts about the direction the community is taking. “The outbreak is moving so quickly that I am worried people will jump and we won’t do the correct research,” he says.

Recalcitrant Mosquito Blamed For Zika’s Spread

With a treatment or vaccine for Zika potentially years away, countries are relying on mosquito control to curb the virus’s spread. Aedes aegypti mosquitoes, which inhabit tropical and subtropical regions, have been named as the culprit in transmitting the virus.

But getting rid of Aedes aegypti is extremely difficult because the mosquitoes don’t seem to be affected by most spraying regimens, says Joseph M. Conlon, an entomologist and technical adviser to the American Mosquito Control Association. According to Conlon, Aedes aegypti feed during the day, but pesticides must be sprayed at dawn or dusk. Also, mosquitoes like to come indoors to feed. So, unless pesticides are sprayed inside homes, chances are good they’re not getting to the insects.

These mosquitoes are very small, and you can’t feel the bites. “Oftentimes you don’t even know you’ve been bitten,” Conlon says.

To get rid of the biting bugs, it’s critical to eliminate any standing water. “I’ve seen Aedes aegypti breeding in discarded soda bottle caps,” Conlon says. “They’re survivors.”

Despite Aedes aegypti’s survival skills, the mosquitoes actually have a fairly limited flight range of about 150 meters. That has made some scientists suspect that because Zika has spread so quickly, the more common Culex mosquito may be transmitting the virus as well. The theory is currently being investigated.

“If that is true, that brings this to a whole different level,” Conlon says. Culex mosquitoes have a much larger range, he notes, but they can usually be controlled through common mosquito abatement programs. ◾

2016 (July 11)

https://cen.acs.org/articles/94/i28/Using-computer-simulations-fight-Zika.html

Using computer simulations to fight Zika

July 11, 2016 | A version of this story appeared in Volume 94, Issue 28