Cory Dobson, Author at Sanford Burnham Prebys - Page 30 of 41

Author: Cory Dobson

Institute News

Mirco Guigli graduates SBP’s PhD program, will continue project at Vala Sciences

Authorjmoore
Date

March 18, 2016

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Mirco Guigli, who defended his PhD thesis on February 25, represents another success for SBP’s graduate program. He not only developed a prototype microscope that has generated commercial interest, but has a clear plan for his future—he will join Vala Sciences to continue this work.

Guigli knew before coming to SBP that he intended to work in industry, which made him a good fit for the laboratory of Jeffrey Price, MD, PhD, an associate professor here and president and CEO of Vala. Price’s lab develops high-performance imaging technologies to support drug screening.

When asked how he decided on SBP for his graduate training, Guigli explained, “Jeff contacted me and suggested I come back to his lab to do a PhD—I had done an internship with him in 2009 as part of my masters program. I was actually pretty happy where I was, working as an electrical engineer designing a dialysis machine for a company in Italy, but I was 25 and had nothing to lose.”

His background in engineering was helpful for Guigli’s project, in which he designed, built, and adapted software for a microscope that offers a promising alternative to confocal microscopy. This system offers similar resolution to confocal, but takes up much less space and uses less intense illumination, allowing imaging of biological processes in real time.

This high resolution is possible because the microscope employs structured illumination, in which portions of the specimen are illuminated in sequential complementary grid patterns. While this approach has already been employed in commercially available microscopes, the key to this new system is the use of a digital micromirror (also used in IMAX projection) to control which parts of the specimen are illuminated. Because digital micromirrors are not microscopic, they’re easier to synchronize with image collection, which could make this microscope faster than what’s currently available.

While this project, focusing on technology rather than biology, is unusual for SBP, Guigli greatly values the knowledge he gained. “I was basically learning what a protein was at age 27. My fellow students, who mostly had experience in biological research, were really helpful. As we were discussing our projects over beers, they really wanted to help me understand their work. From those discussions, I also got a feel for biology as a whole, since they’re working on everything from HIV to muscle regeneration to Alzheimer’s.”

Institute News

SBP scientists join race for a cure

Authordrobison
Date

March 17, 2016

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Andrew Carley, PhD, has a personal motivation for finding a cure for diabetes. As one of the 29 million Americans with diabetes, he became a biomedical researcher to better understand the causes of disease.

For Julio Ayala, PhD, a passion for medical research was sparked by his grandmother, a type 1 diabetic, who at age 86 has successfully managed the disease most of her life.

Julio Ayala, PhD
Julio Ayala, PhD

Siobhan Malany, PhD, is an avid cyclist who believes so strongly in team efforts that she has enlisted robots to join her research team searching for new drugs to fight disease.

On Sunday, March 13, 2016, these Sanford Burnham Prebys scientists took their interest in biomedical research to the roadways of Central Florida as they joined 1,100 participants in the 2016 Tour de Cure at Lake Nona bicycle ride for diabetes. The twelve-member SBP team collectively pedaled more than 400 miles and raised $9,000 to fight the disease. Participants began the 25, 63, and 100-mile courses in Lake Nona Medical City near SBP and the Center for Metabolic Origins of Disease, the site where researchers study diabetes in hopes of identifying new, more effective therapies.

“It was a fun way to give back and do what I love to do.  Cycling has been my commute, my sport and my escape —now it’s a way to contribute,” said Malany, who completed the 100-mile course in five hours. She enjoyed the camaraderie and credited the group with a bit of competitive motivation. “I kept a 21.5 mile per hour pace, which was not something I would have accomplished had I been cycling alone. It was fast and fun being in a pack because you conserve energy by drafting,” added Malany.

Siobhan Malany, PhD
Siobhan Malany, PhD

Since moving to Lake Nona in December from Chicago, Carley has gotten back into cycling and now bikes to the Institute in Medical City each day. He completed a Century ride to mark the 20th anniversary of the Tour de Cure in 2011 in Chicago and decided to mark the 25th anniversary of the event with a 25 mile ride. “I selected the 25 mile course because it was the maximum length of time my 3-year old daughter would remain content in her bike stroller watching a Toy Story movie. She weighs only 32 pounds and the course was relatively flat so we were able to complete the ride in two hours despite frequent stops,” said Carley.

Tour-de-cure

Team captain Ayala participated in various ADA and JDRF fund raising events while at Vanderbilt University. “While riding my bike to work a few years ago, I saw the first Tour de Cure in Lake Nona and knew that I wanted to participate. We study diseases of metabolism at the Medical City site and a number of faculty, including me, receive ADA-funded grants, so I wanted to get involved,” said Ayala.

Ayala credits the team’s spirit with providing extra motivation to push through the extreme winds encountered on the course. It’s with similar determination that they approach their daily race for the cure in their research labs.

Institute News

Research points to new ways to treat inflammatory bowel diseases

Authorjmoore
Date

March 16, 2016

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A new paper in Nature co-authored by SBP’s Randal Kaufman, PhD, reveals how briefly reducing dietary amino acids could help patients with inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. The research shows for the first time that a specific amino acid sensor controls gut inflammation.

These results, generated in the laboratory of Bali Pulendran, PhD, of Emory University, could also lead to new drugs for IBD, which are sorely needed—currently available drugs don’t work for many patients.

What was known before this study

The amino acid sensor studied, GCN2, is one of four sensors that activate the integrated stress response (ISR) (the other sensors respond to different types of cellular stress). Activation of the ISR alters gene expression in ways that help cells survive: facilitating efficient utilization of nutrients, combating oxidative stress, and repairing DNA damage. While previous research had shown that the ISR helps limit gut inflammation, this is the first to implicate GCN2.

Significance

The findings “highlight the capacity of the immune system to sense and adapt to environmental changes, such as nutritional starvation, that cause cellular stress,” said Kaufman.

“This response may have evolved as a negative feedback mechanism to limit inflammation. This mechanism ensures that sufficient building blocks are available for the tissue regeneration required to repair the damage caused by inflammation and prevents the immune response from getting out of control.”

Implications for IBD

While GCN2’s anti-inflammatory activity can be triggered by a low-amino acid diet, reducing protein intake is not a feasible long-term treatment for IBD because it would generally impair the immune system. If human studies confirm that GCN2 is also protective in human disease, drugs that target GCN2 or later steps in the ISR could be developed to treat IBD.

Next steps

“We plan to investigate whether this pathway is involved in regulating other types of inflammation. If it is, this discovery could be important for treating other diseases like rheumatoid arthritis or multiple sclerosis,” Kaufman added.

The paper is available online here.

Institute News

Super advanced microscopy reveals how cellular anchors are activated

Authorjmoore
Date

March 15, 2016

micrographs and corresponding models of integrin shape

Integrins are indispensable cell-surface proteins that form bridges with the surrounding protein matrix and other cells. They also transmit the biochemical and mechanical signals that regulate essential cellular processes, such as proliferation, differentiation, migration and cell death. Understanding how integrins become activated is important for developing ways to modulate their function, which is relevant to many disease processes, including cancer, autoimmunity, and fibrosis (hardening of tissue).

The laboratory of Dorit Hanein, PhD, in collaboration with Niels Volkmann, PhD, both professors in SBP’s Bioinformatics and Structural Biology Program, have made an important contribution in this area. Their recent study fundamentally changes our understanding of how integrins are activated—instead of a binary one-step process, it turns out to be a much more nuanced process involving multiple states.

The details

Publishing in the Biophysical Journal, the team used cryo electron microscopy (cryoEM) and advanced computational methods to determine the three-dimensional structures of full-length human integrin, αIIbβ3, which mediates blood clotting. CryoEM allows scientists to look at how a protein works in a near-physiological environment—surrounded by water and interacting with other proteins.

“Because cryoEM captures multiple states, we were able to show that the activation of integrins is much more complex than we thought—they exist in an equilibrium of conformations between bent and upright, and binding to their partners makes them more likely to straighten. Also, the matrix-binding domain is accessible even in the bent form, making it clear how integrins can be initially activated by extracellular signals,” explained Hanein.

Until now, the model for integrin activation was based on structures generated using other techniques that have value, but significant drawbacks as well. For example, X-ray crystallography constrained the protein to a highly compact and bent conformation, which implied an inactive configuration. Another type of electron microscopy revealed an upright conformation, assumed to be the active form that’s triggered by a one-step switch.

What the results mean

The new model aligns better with integrins’ ability to integrate multiple signals to control key cell processes. Instead of one binding event turning the integrin all the way on, each additional signal shifts it towards the upright form, which transmits mechanical signals more easily.

This refinement of the model is critical for designing and interpreting experiments involving integrins. According to Volkmann, “To do translational research, you have to understand the language, and in this case the language is structure.”

The paper is available online here.

Institute News

New drug combination may lead to treatment for childhood brain cancer

AuthorJessica Moore
Date

March 14, 2016

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Researchers at SBP have identified a new combination therapy for the most aggressive form of medulloblastoma, a fast growing type of pediatric brain cancer. The study, published  in Cancer Cell, is expected to lead to a clinical trial to confirm the benefits of the novel drug combination. Continue reading “New drug combination may lead to treatment for childhood brain cancer”

Institute News

Scientists find optimal method for generating regulatory T cells to treat autoimmune disease

Authorjmoore
Date

March 11, 2016

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While we normally think of T cells as recognizing invaders, their roles are more complex. For example, some T cells, called regulatory T cells (Tregs) suppress conventional T cells’ immune responses. Because conventional T cells can escape normal controls and drive autoimmune diseases such as rheumatoid arthritis and type 1 diabetes, as well as rejection of transplants, Tregs are increasingly viewed as a way to rein in autoimmune diseases. Continue reading “Scientists find optimal method for generating regulatory T cells to treat autoimmune disease”

Institute News

Study triples the number of known cases of a rare disease

Authorjmoore
Date

March 10, 2016

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A recent paper from the laboratory of Hudson Freeze, PhD, characterizes 39 previously unreported cases of a specific type of congenital disorder of glycosylation (CDG). CDGs, the focus of research in Freeze’s lab in SBP’s Sanford Children’s Health Research Center, are rare inherited disorders. CDG symptoms, which can include developmental delay, movement problems, and impaired function of multiple organs, differ depending on the underlying mutation. Continue reading “Study triples the number of known cases of a rare disease”

Institute News

Upcoming symposium: Cancer Immunology and the Tumor Microenvironment

Authorjmoore
Date

March 10, 2016

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On March 17, SBP La Jolla is hosting a symposium on the interactions between the immune system and tumors, including how they can be leveraged for cancer treatment. The symposium is organized by Carl Ware, PhD and Robert Rickert, PhD, the directors of the Inflammatory and Infectious Disease Center and the Tumor Microenvironment and Cancer Immunology Program, respectively, and features presentations by leaders in the field:

Crystal Mackall, MD, Stanford University

Yang-Xin Fu, MD, PhD, UT Southwestern

Mikala Egeblad, PhD, Cold Spring Harbor Laboratory

Linda Bradley, PhD, Sanford Burnham Prebys Medical Discovery Institute

Jose Conejo-Garcia, MD, PhD, Wistar Institute

Jonathan Powell, MD, Johns Hopkins School of Medicine

Shannon Turley, PhD, Genentech

Karen Willard-Gallo, PhD, Institut Jules Bordet – Belgium

Sandip Patel, MD, UC San Diego

Adam Godzik, PhD, Sanford Burnham Prebys Medical Discovery Institute

The symposium will be held from 9-4:30 in Fishman Auditorium (overflow seating in the Building 12 auditorium), with a reception to follow. If you plan to attend, please register here.

Institute News

Targeting gut microbes may help malnourished children grow

Authorjmoore
Date

March 7, 2016

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Malnutrition in infants and young children can have major life-long impacts—deficiencies in important nutrients stunt growth and impair development. Although aid organizations have developed fortified meals to make up for these deficiencies, they don’t completely compensate for the lack of nutrition. Now scientists know why malnourished children might not benefit as much as they should from added nutrients in their diet. Continue reading “Targeting gut microbes may help malnourished children grow”

Institute News

The science of crowdfunding

Authorkcusato
Date

March 3, 2016

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He doesn’t need money to produce an album. He’s not raising funds to start a new business in his hometown. And he’s not asking for cash because he’s a famous rapper who suddenly finds himself “bankrupt.” He is a young scientist who needs money to conduct research aimed to save lives, so he is turning to crowdfunding.

Joseph Lancman, PhD, is a scientist in the organogenesis lab of Duc Dong, PhD, at Sanford Burnham Prebys Medical Discovery Institute (SBP) in La Jolla. Lancman’s crowdfunding site just went live on Diabetes Research Connection (DRC), a San Diego-based company that created a platform to connect donors directly with early-career scientists. In the next 90 days, Lancman hopes to generate $50,000 for his research project that may provide the scientific breakthrough needed to find a cure for type 1 diabetes. Watch his video here.

“We recently discovered a way to reprogram cells and change their identity without removing them from the body,” Lancman said. “We believe this breakthrough will have great implications for people with degenerative diseases, like diabetes.”

As many as three million Americans have type 1 diabetes.  Millions of children and adults struggle with this disease, yet funding has decreased dramatically for research. In fact, the head of the National Institutes of Health (NIH)  said last year that young scientists in this country now face the worst funding in 50 years.

So, if you are a young scientist with a great idea, where do you go? Alberto Hayek, MD, co-founder and president of the DRC and world-renowned diabetes expert, says some go away. “Due to the limited funding available, scientists just starting out in their career are forced to leave the field of diabetes and go to fields that have more funding. We are giving scientists the funding needed to test and validate research that departs from conventional thinking,” Hayek said.

Dong says his lab heard about DRC from others in the field. “The DRC is committed to funding innovative projects that may not be considered mainstream approaches. The crowdfunding model itself is highly innovative, by making sure that 100% of donations will go directly into specific labs and projects chosen by the individual donors,” Dong said.

And it works. Since DRC launched its platform in 2014, six research projects from all over the country have been 100% funded. Every dollar of the money raised goes directly to the scientist. The power to fund projects has been given to the people.

Lancman has a total of 90 days to make it happen. He needs 5,000 people to donate $10 each in order to reach his goal. He’s excited to be able to continue to work towards a cure for diabetes, and allow people to live full lives without painful daily insulin injections.

Come on, social media.