Research led by Suresh Alahari, PhD, the Fred Brazda Professor of Biochemistry and Molecular Biology at LSU Health New Orleans School of Medicine, has found a new role for a protein discovered by his lab in preventing the growth and spread of breast cancer. The results of the study, which could have a significant impact on cancer therapy, are published in the OnlineFirst section of the journal Cancer Research, available here.
Dr. Alahari discovered the novel protein, Nischarin, which is involved in a number of biological processes including the regulation of breast cancer cell migration and movement. Although his lab has shown that Nischarin functions as a tumor suppressor, research continues to uncover new information that may lead to better treatments.
In the current study, the research team investigated Nischarin’s function in exosome release. Exosomes are nano-sized vesicles (fluid-filled sacs) containing proteins, genetic and other material involved in both physiological and pathological processes. Tumor-derived exosomes contain various signaling messengers for intercellular communication involved in tumor progression and metastasis of cancer. Tumor exosomes influence the interactions of various types of cells within the tumor microenvironment, regulating tumor development, progression and metastasis. Primary tumors release exosomes that can enhance seeding and growth metastatic cancer cells.
Among the researchers’ findings: Nischarin regulates cell attachment and alters the properties of exosomes. Exosomes from Nischarin-positive cells reduce breast cancer cell motility and adhesion, as well as tumor volume. Nischarin-positive cells release fewer exosomes, and cell survival is decreased. Co-culturing breast cancer cells with Nischarin-positive exosomes decreases tumor growth and lung metastasis.
“This novel role for the tumor suppressor Nischarin not only increases our understanding of the exosome biology, but can be translated to identifying new targets for modulating cancer metastasis,” notes Dr. Alahari. “Inhibition of the secretion of exosomes may serve as an effective treatment for cancer.”
In the news
According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, which includes data from LSU Health New Orleans’ Louisiana Tumor Registry, breast cancer represented 15.3% of all new cancer cases and 6.7% of all cancer deaths in 2018. There were an estimated 266,120 new cases of breast cancer in the US and an estimated 40,920 deaths.
“It has been shown that exosomes can be developed as carriers for delivering drugs,” Alahari adds. “Nischarin-expressing exosomes in combination with drugs will likely have very good therapeutic effect on breast cancer patients.”
Other members of the LSU Health New Orleans research team were Drs. Mazvita Maziveyi and Shengli Dong in the School of Medicine’s Department of Biochemistry and Molecular Biology, as well as Dr. Donald Mercante in the School of Public Health’s Department of Biostatistics. The research team also included scientists from Central University of Punjab, Louisiana State University, Wayne State University, Xavier University and University of Texas Southwestern Medical Center.
The research was supported by funding from the Fred Brazda Foundation and LSU Health New Orleans School of Medicine.
New Orleans, LA – Research led by Suresh Alahari, PhD, Fred Brazda Professor of Biochemistry and Microbiology at LSU Health New Orleans, suggests a novel protein may be a promising therapeutic target to treat or prevent metabolic disorders. The study also reported for the first time metabolic distinctions between male and female mice. The findings are published in the December 2018, issue of the International Journal of Obesity, available here.
The researchers conducted studies in both a mouse model and in human tissue to advance our understanding of the role of Nischarin, a novel protein discovered by the Alahari lab, in fat distribution and insulin resistance leading to diabetes and obesity. Nischarin functions as a molecular scaffold and is involved in the insulin signaling pathway.
“Nischarin disruption resulted in insulin resistance in female mice, but not in male mice, suggesting that Nischarin protects against diabetes in females,” notes Dr. Alahari. “Our human data indicate that Nischarin expression is suppressed in fat tissue of obese humans. Higher expression of Nischarin correlates with lower BMI and improved glucose and lipid metabolism.”
Working with experimental Nischarin-mutant as well as wild mice fed chow and high-fat diets, the researchers found gender differences in body fat distribution, increased insulin resistance and decreased glucose tolerance in the females.
To link the work in mice with human disease, the scientists also studied paired samples of human subcutaneous and visceral fat that were obtained from 400 individuals (267 women, 133 men), ranging in age from 19 to 93 years, with BMIs from 18.9 to 78.9 kg/m². The research team found that Nischarin expression was lower in both visceral and subcutaneous adipose tissues of individuals with obesity. The majority of parameters associated with obesity – impaired glucose and lipid metabolism as well as insulin resistance – were inversely correlated with Nischarin expression, as were weight, waist circumference and waist-hip ratio. They also found that Nischarin expression was higher in the visceral fat.
According to the Centers for Disease Control and Prevention, the age-adjusted percentage of US adults who were obese or had been diagnosed with diabetes rose in all states from 1994-2015. “In 1994, all but two states had prevalence of obesity less than 18% and no state exceeded
22%. In 2015, no state had less than 18% and all but one state exceeded 22%. Similarly for diagnosed diabetes, in 1994, no state had prevalence less than 6.0%. In 2015, all states exceeded 6.0%; 27 of these exceeded 9.0%.”
“Understanding how Nischarin in adipose tissues influences metabolic dysfunction might warrant a new paradigm in metabolic studies,” Alahari concludes.
Besides LSU Health New Orleans School of Medicine, participating institutions included the University of Leipzig in Germany and Tulane University School of Medicine.
The research was supported by funds from LSU Health New Orleans School of Medicine and the Fred Brazda Foundation, as well as grants of the Deutsche Forschungsgemeinschaft, Obesity Mechanisms (SFB 1052, B01).
Congratulations to Aliyah Pierre from Dr. Rinku Majumder's Lab who won 3rd place in the annual research competition by REU National Science Foundation.
New Link Between Hypoxia and Thrombosis
A team of researchers from the department of Biochemistry, LSU Health Science Center, New Orleans, School of Medicine and University of Massachusetts Medical School, led by Rinku Majumder, PhD, Associate Professor of Biochemistry at LSUHSC just published an article in the prestigious journal "Blood"( https://doi.org/10.1182/blood-2018-04-841585).
This group has shown by biochemical and genetic approaches that decrease in concentration of a body's natural anticoagulant, Protein S, is responsible for increased thrombotic risk at low oxygen condition (hypoxia). The journal editorial board has come out with a commentary on this topic (https://doi.org/10.1182/blood-2018-06-854976) and observed-"This is an important contribution to our understanding of the molecular basis of the augmentation of thrombosis by hypoxia." Hypoxia is common in many disease states, including cancer. However, hypoxia mediated potentiation of thrombotic episode due to down regulation of a body's natural anticoagulant, protein S is novel. This article is also selected as one of the featured articles on the cover page of the issue.
Other members of the research team include Dr. Vijaya S. Pilli, Mr. Arani Datta and Dr. Sadaf Afreen from LSUHSC and Ms. Donna Catalano and Dr. Gyongyi Szabo of Umass Medical Center.
Research led by Suresh Alahari, PhD, Professor of Biochemistry and Molecular Biology at LSU Health New Orleans School of Medicine, has shown for the first time that a tiny piece of RNA deregulates energy metabolism, an emerging hallmark of cancer. The finding identifies a new target for therapeutic intervention in breast cancer. The research is published in Molecular Cancer.
Sunyoung Kim, founder of Chosen Diagnostics Inc, was selected by the State Department and Small Business Administration in Washington DC to be one of the 300 US delegates to the Global Entrepreneurship Summit (GES) in Hyderabad India. A LSU Health spin-out company, Chosen Diagnostics provides diagnostic tests that can personalize and improve infant health. GES serves as a link between governments and the private sector and champions new opportunities for investment. Over 1000 delegates from 150 countries attended the meeting in Hyderabad, India from November 28-30, 2017. Participants are picked for their ability to catalyze innovation, investment, and mentoring. The focus of this eighth annual summit was supporting women entrepreneurs, addressing some of the most intractable global challenges, and fostering economic growth globally. Ivanka Trump headlined the United States delegation and Indian Prime Minister Narendra Modi headed the delegation from the host country.
Congratulations to Dr. Joseph Chaney for his appointment as an Assistant Professor of Chemistry at Xavier University!
Alahari Lab in the News
Research led by Suresh Alahari, PhD, Fred Brazda Professor of Biochemistry and Molecular Biology at LSU Health New Orleans School of Medicine, has demonstrated the potential of a protein to treat or prevent metabolic diseases including obesity and diabetes. The lab's findings have been published online in the Journal of Biological Chemistry; and, more recently, have been featured on Fox 8 News and other local news stateions.
Follow the link below to see the video from Fox 8 News:
Journal of Biological Chemistry
Dr. Alahari and his lab have been featured in the latest version of The Journal of Biological Chemistry for their groundbreaking research on obesity and diabetes. A number of other news sources have also recently published this article (see below). Congratulations to the entire Alahari Lab on this accomplishment!
LIFT2 Grant Award
The Board of Supervisors of Louisiana State University and Agricultural and Mechanical College has established the "Leveraging Innovation for Technology Transfer" (LIFT2) Grant program to support the furtherance of innovation and commercialization through proof-of-concept research.
On May 3, 2017 Dr. Desai and her lab received a $50,000 LIFT2 award to continue their current research. This grant was awarded to help fund her research project titled: "ISGylation: a potential diagnostic/prognostic biomarker for neurodegenerative diseases." Congratulations to Dr. Desai and her lab on this accomplishment!
Biz The Magazine - May 2017
Dr. Sunyoung Kim and her startup company, Chosen Diagnostics, were featured on the cover of the May 2017 issue of Biz New Orleans The Magazine. In the article, Dr. Kim reflects on what it takes to build a healthcare startup and why Louisiana is the right place for it to take shape.
In November, Chosen Diagnostics won the $25,000 grand prize at the 2016 BioChallenge Startup Competition, an annual event organized by the New Orleans BioInnovation Center to identify and support local life sciences startups. She is the first woman to win the award.
On the heels of that success, the company took top honors in the 2017 JEDCO Challenge, held this past March during New Orleans Entrepreneur Week. The win included a $60,000 prize package. Judging panels weren’t the only ones who recognized the company’s merit — in both competitions, Chosen Diagnostics won the “crowd favorite” prizes as well.
NPR Out to Lunch
Dr. Sunyoung Kim was a featured guest on NPR's "Out to Lunch" program on March 2, 2017. During the interview, Dr. Kim discussed a new test her lab is working on that will help diagnose Necrotizing Entercolitis (NEC) in newborn babies. NEC is a condition primarily seen in premature infants and is the second most common cause of morbidity for the vulnerable population. Current tests are only about 40% accurate and only work after clinical symptoms develop. An NEC diagnosis can easily overwhelm parents who may already be having a hard time with the unexpected early arrival of their child. Developing a test that allows for detection of NEC before symptoms develop is a huge leap forward for Neonatologists. Early diagnosis and intervention will improve outcomes for the affected infants.
You can listen to Dr. Kim's interview in full by clicking on the following link:
Most Cited Journal Article: Molecular Cancer
Congratulations to Dr. Alahari and his lab team on publishing the most cited article of 2016 from the open access journal, Molecular Cancer. This is a great honor for Dr. Alahari, as Molecular Cancer is one of the most prestigious scientific journals, with a 5.9 impact rating.
A link to the article can be found here:
Silvia Juliana Serrano-Gomez, Mazvita Maziveyi, and Suresh Alahari
Prestigious NSF I-Corps Award
Congratulation Dr. Sunyoung Kim on this great news: https://www.eurekalert.org/pub_releases/2016-12/lsuh-tfe120116.php
NSF awarded LSU Health New Orleans a $50,000 grant so the LSU Health New Orleans reasearchers led by Dr. Kim can participate in the national NS Innoviation Corps (ICorps) Program in January 2017.