In The News
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).
Alahari Lab Christmas 2018
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.
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!
Dr. Suresh Alahari received the 2016 Outstanding Service to the Community Award for selfless acts that benefit the School of Medicine and those served by the School of Medicine.
Research led by Dr. Suresh Alahari, the Fred Brazda Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans and its Stanley S. Scott Cancer Center, details exactly how the Her2 cancer gene promotes the progression and spread of breast cancer cells. read more...
Newly Discovered Protein Discovered May Suppress Breast Cancer Growth Science Daily (Sep. 15, 2011) — Research led by Suresh Alahari, PhD, the Fred Brazda Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans and its Stanley S. Scott Cancer Center, has found that a protein discovered by his laboratory can inhibit the growth of breast cancer cells. The research is published September 14, 2011 online in the Journal of the National Cancer Institute. Building upon Dr. Alahari's earlier discovery of nischarin, a novel protein that regulates breast cancer cell migration and movement, this current study examines the presence and levels of nischarin in breast cancer tumor tissue from 300 women as well as normal breast tissue samples. The researchers also generated derivatives of human metastatic breast cancer cells to test by manipulating the protein in a mouse model. "We found that normal human breast tissue samples had statistically significantly higher levels of nischarin compared with tumor tissue samples," notes Dr. Alahari, "and tumors grew significantly faster in the cells where we blocked the production of nischarin. Tumor growth and metastasis were also reduced in the samples where we manipulated the overproduction of nischarin. Our research shows that nischarin can function as a tumor suppressor of breast cancer, inhibiting breast cancer progression. "The research team also describes the regulation of nischarin and reports the genetic mechanism by which this protein suppressed breast tumor growth, information that could be used to target new treatment approaches. Excluding skin cancer, breast cancer is the most common type of cancer among women in the United States. The National Cancer Institute estimates 230,480 new cases among American females this year, and 2,140 among men in the US, with 39,520 deaths in women and 450 deaths in men. Risk factors include aging, weight gain, combined hormone therapy, physical inactivity, and consumption of one or more alcoholic beverages per day. A family history increases risk, as does never having had children or having a first child after age 30. Mammography can often detect breast cancer at an early stage when treatment options are greatest and a cure is possible. "Next steps include determining whether nischarin controls some of its tumor suppressor roles through regulation of the pathways we reported in this paper," concludes Dr. Alahari, "and these studies are already underway. "The LSUHSC research team also included Dr. Robin McGoey, Associate Professor of Pathology, as well as postdoctoral fellows, Drs. Somesh Baranwal, Yanfang Wang, Rajamani Rathinam, and Lianjin Jin, Researchers from Duke University and Memorial Sloan Kettering Cancer Center also contributed. The research was supported by grants from the National Institutes of Health, the Susan Komen Foundation, the Louisiana Board of Regents, and the Louisiana Cancer Research Consortium.