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From cancer and sepsis to COVID-19: the various functions of galectin 1, a key protein in the human body

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The future doesn’t have to be finely defined after graduating from college. Gabriel Rabinovich received an honors degree as a biochemist from the National University of Córdoba. He went to do a course in Israel, but when he returned he did not know what to do with his life. It was not even clear whether he wanted to pursue a Ph.D. and pursue research. He joined a chair at the university. He did lots of experiments that didn’t work. He got frustrated. He went into crisis. But he still went ahead with the detailed study of the functions of a protein, galectin 1, which is in the cells of the human body. Today at age 52, Rabinovich is one of the most cited scientists from Argentina in the world for his discoveries, and he has just published a new work that can help humanity better cope with sepsis, a condition generated from an infection that kills 11 million people per year.

Rabinovich has 290 published jobs. But the last paper, which was reviewed and accepted by the prestigious magazine Nature Immunology, was one of the works that “fell in love with him the most because it answers two important enigmas”, as he told Infobae. In collaboration with researchers from the United States, Rabinovich and his team identified a mechanism by which the protein galectin 1 – which he has been studying since 1993 – participates in the inflammatory response that causes a patient to suffer from sepsis and is difficult to control when the antibiotics no longer respond.

By doing the research, a new molecular target was provided that can be targeted with future research to develop better diagnoses and treatments, and a potential drug has already been tested in animals -with good results- that could be effective in counteracting generalized inflammation that occurs as a result of an infection. The drug is a monoclonal antibody that Rabinovich had developed with his team, patented to treat cancers refractory to other therapies, and published in the journal Angiogenesis.

Rabinovich's team found that galectin operates as an alarm signal that warns the immune system that it must increase the inflammatory response since there is an infection by a germ

Last september, The World Health Organization (WHO) had called for attention to sepsis, which appears in response to an infection. “If it is not recognized in time and is managed promptly, can lead to septic shock, multiple organ failure, and death. Critically ill patients with a severe form of COVID-19 and other infectious diseases are at greater risk of progressing to sepsis and dying, ”the health agency had warned. Plus, sepsis survivors aren’t out of the woods either – only half make a full recovery.. Many affected by sepsis have been women who have undergone clandestine abortions or infections derived from a caesarean section. It is also known that half (49%) of patients with sepsis cared for in intensive care units contracted the infection in hospital. Due to this situation, the development of better treatments for sepsis is key today.

That global public health concern is related to galectin 1. “It is a protein that is in various systems of the human body and binds to sugars. It is in the muscles, in the brain, in the immune system. She can be like a villain or like a heroine depending on the context ”, explained Rabinovich, who is a senior researcher at the Institute of Biology and Experimental Medicine of Conicet and the Faculty of Exact and Natural Sciences of the University of Buenos Aires, and a foreign member of the United States Academy of Sciences.

Regarding sepsis and after five years of work with Vijay Rathinam, scientist at the Department of Immunology at UConn Health in the United States, Rabinovich’s team found that galectin operates as an alarm signal that warns the immune system to increase the inflammatory response since there is a germ infection. Thus, the protein amplifies that response of the immune system, sepsis develops and more damage occurs in the tissues and organs of the body. “It plays a pivotal role for sepsis to develop,” he emphasized.

Rabinovich has already unraveled the other roles that galectin plays in natural situations such as pregnancy and in other diseases as varied as different cancers (Shutterstock)

Rabinovich carried out different experiments to demonstrate this together with Argentine researchers Santiago Méndez Huergo and Juan Manuel Pérez Sáez and their American collaborators. An experiment was done with mice that were produced in the laboratory with deficiencies in the levels of galectin 1. Those animals were later infected by bacteria. Being deficient in the protein, the sepsis picture generated was more reduced compared to those with normal levels of the protein.

They also tried giving the monoclonal antibody to animals with sepsis and found that it could control it.. “One of the next challenges will be to start clinical trials with the monoclonal antibody in patients with sepsis who do not respond to other treatments. It will serve to evaluate efficacy and safety ”, he commented. For the work on sepsis, it had funding from the National Agency for Scientific Promotion, Technological Development and Innovation, the Bunge y Born Foundation, the Sales Foundation and families who are interested in scientific research and make donations.

In addition to the novelty for sepsis, the scientist, who has won countless awards such as the “Investigator of the Nation” from the Ministry of Science, Technology and Innovation of Argentina, has already unraveled the other roles that galectin plays in natural situations such as pregnancy and in other diseases as varied as different cancers, sexually transmitted infections, parasitic diseases like Chagas, and autoimmune diseases like multiple sclerosis and rheumatoid arthritis, and for diabetes.

The scientist has won countless awards such as the

In some cases, protein is the big baddie. In others, the heroin that comes to help the body. In cancers, galectin 1 helps cancer cells escape the immune response and migrate to other parts of the body, causing metastasis. In this case, it plays a detrimental role against the survival of the human organism, as also occurs in cases of infection that triggers sepsis. Therefore, the monoclonal antibody that was now tested for sepsis had been studied as an inhibitor in pre-clinical studies in tumor-bearing animals.

In the case of pregnancy, which is a natural physiological situation, protein also fulfills its role. When the protein is expressed in the placenta, it stops the mother’s cells (lymphocytes) from attacking the fetus, which has genetic material from the father. Galectin kills maternal lymphocytes that try to harm the fetus. Women with recurrent miscarriages have been found to have decreased galectin 1 levels. In animal experiments, when they inject a drug that mimics the function of galectin, the frequency of miscarriages is reduced. This means that galectin plays a beneficial role in the advancement of pregnancies.

In relation to autoimmune diseases, the protein galectin 1 is capable of eliminating lymphocytes that cause damage to the nerves of the brain. Something similar happens with lymphocytes that damage the joints in rheumatoid arthritis, and in those that affect the pancreas in diabetes. In these cases, when there are low levels of the protein, there is a greater risk of developing these diseases.

Sepsis is a condition caused by an infection that kills 11 million people per year.

How does Rabinovich see the young man who was in Córdoba and in crisis when he started? “While it is always said that crises are opportunities, I feel like I have experienced it. Science, friends and my family have saved my life. Many have helped me move on and build the puzzle of the functions of the protein galectin 1. We are bringing new fundamental knowledge to give people therapeutic options. I choose every day to provide knowledge and work in collaboration with other researchers ”, he stressed.

In a pandemic, he kept working. With meetings at Zoom and in the lab. He is developing studies on immunology and COVID-19 with the support of the Edenor Foundation and the Bunge y Born Foundation. “We seek to elucidate aspects of the immune system when a person is affected by the coronavirus and causes the COVID-19 disease,” he explained. “I always follow the idea that if something can be dreamed, it can be done. But you also need support for young people and give them the opportunity as I have had ”.


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