Today, we take a closer look at LUTED Lab, led by Prof. Dr. Fabiola Zakia Mónica. The laboratory conducts research focused on lower urinary tract symptoms and erectile dysfunction. Currently, it develops projects aimed at drug repurposing, a strategy that seeks to identify new therapeutic applications for drugs that are already marketed and prescribed.
To better understand these projects, we spoke with Prof. Fabiola, master’s student Mariana Burille Moretti, and postdoctoral researchers Dr. Gabriela Reolon Passos and Dr. Guilherme Ruiz Leonardi.
The path that led to the creation of LUTED Lab
The head of LUTED Lab, Dr. Fabiola Mónica, has been a professor in the Graduate Program in Pharmacology since 2011. She holds a degree in Pharmacy from the Pontifical Catholic University of Campinas and a PhD in Pharmacology from UNICAMP. She completed her postdoctoral training at George Washington University under the supervision of Prof. Ferid Murad, recipient of the 1998 Nobel Prize in Physiology or Medicine. Between 2019 and 2021, she was a member of the scientific committee of the Brazilian Society of Pharmacology and Experimental Therapeutics.
Prof. Fabiola completed her PhD under the supervision of Prof. Dr. Edson Antunes, also from the Graduate Program in Pharmacology. Since then, she has investigated the pharmacology and pathophysiology of the lower urinary tract. This line of research led her to establish LUTED Lab.
The connection between urinary symptoms and erectile dysfunction
The LUTED Lab’s focus on both the lower urinary tract and erectile dysfunction is no coincidence. Complications in the lower urinary tract can lead to urinary symptoms, including those affecting urine storage (such as nocturia, when a person wakes up at night to urinate), voiding (such as straining to urinate), and the post-voiding phase (such as dribbling after urination). The LUTED Lab’s decision to study both the lower urinary tract and erectile dysfunction is intentional, as these conditions are strongly related. Approximately 70% of men with lower urinary tract symptoms also experience erectile dysfunction.
This relationship occurs because both mechanisms are regulated by the same pathways in our body. Prof. Fabiola explains: “When we think about bladder relaxation, we are referring to the Sympathetic Nervous System. For bladder contraction, the Parasympathetic Nervous System. In the case of the corpus cavernosum, we have the Sympathetic Nervous System, which causes relaxation, but also nitric oxide. In the prostate, we are talking about nitric oxide.”
The Sympathetic and Parasympathetic Nervous Systems, along with nitric oxide, are different pathways that coordinate activities in our body. It is as if they were departments within a company responsible for different functions. Sometimes, the same department coordinates more than one function. For example, HR may be responsible for hiring and payroll.
Like any department, these systems may face problems, such as having fewer “staff” due to illness. When this happens, delays may occur not only in hiring but also in payroll. The same happens in our body. If the Sympathetic Nervous System is impaired, it may affect not only bladder relaxation but also the corpus cavernosum, a process that is important for the end of penile erection.
Impacts on quality of life and main risk factors
The presence of urinary dysfunction associated with erectile dysfunction greatly affects patients’ quality of life. Urinary symptoms have a more direct impact, as explained by Prof. Fabiola: “As the condition worsens, it can even lead to involuntary urine leakage in public. People may feel embarrassed to go out and drink less water. Depending on the severity of urinary incontinence, they may even need to use diapers.”
Symptoms that affect sexual performance primarily impact men. Prof. Fabiola comments: “For women, since we visit a gynecologist from a young age, this is less of a taboo. But for men, issues related to masculinity have a strong impact.”
Lower urinary tract symptoms are especially common after the age of 40. The main cause is aging itself. “In women, this is less studied. But we know, for example, that perimenopause can affect the pelvic floor. So, I would say the main causes are hormonal factors and aging. In men, it is mainly related to the prostate. We know that aging and prostate hyperplasia are the main factors,” explains Prof. Fabiola.
She also highlights that prostate growth is itself linked to aging: “Age is still the main factor, especially when associated with comorbidities such as obesity and diabetes. These conditions lead to a state of chronic and persistent inflammation, which induces growth factors that, in turn, cause prostate hyperplasia.”
New uses for old drugs
When studying treatments for these conditions, LUTED Lab adopts a strategic approach: drug repurposing. From this perspective, researchers do not aim to create a drug from scratch. Instead, they seek to investigate the therapeutic potential of drugs that are already available on the market, but now for the treatment of new diseases.
Prof. Fabiola explains that this approach has several advantages: “It is a drug that is already in clinical use and has been approved in studies required by regulatory agencies. So, its safety and efficacy have already been demonstrated for a given treatment. This makes the process cheaper, as it saves development time.”
Prof. Fabiola had already been working with drug repurposing even before the term became popular. She explains that, since the beginning of her career, she has been conducting research in this area: “Basically, we would take drugs already used in the clinic and test them.”
Today, there are several successful examples of repositioned drugs. Perhaps some of the most well-known are Ozempic and Mounjaro. They were initially developed for the treatment of type 2 diabetes, but are now also used in cases of obesity.
Investigating the repurposing of probenecid
As LUTED Lab focuses on lower urinary tract symptoms and erectile dysfunction, it seeks to reposition drugs with potential for these treatments. Currently, Prof. Fabiola leads a FAPESP-funded project (grant no. 24/03517-9) investigating the repurposing of probenecid. In this line of research, postdoctoral researcher Dr. Guilherme Leonardi (grant no. 23/12406-3) and master’s student Mariana Moretti are involved.
Mariana explains her project: “In short, I study the pharmacological repurposing of probenecid. It is an old drug that has been used for a long time to treat gout. Now, I am investigating a new possible clinical application for the treatment of benign prostatic hyperplasia.”
Dr. Guilherme also investigates the repurposing of probenecid, but applied to other treatments. He explains: “The objective of the research is to evaluate the effect of probenecid on organs of the lower genitourinary tract (bladder, prostate, and corpus cavernosum), aiming at a possible repurposing of this drug for the treatment of underactive bladder, overactive bladder, and erectile dysfunction.”
But why invest specifically in the repurposing of probenecid? Its main indication is for the treatment of gout, as it increases uric acid excretion. However, it can also interfere with several other pathways in our body.
This diversity of actions has already led to its repurposing in other contexts. Prof. Fabiola comments: “In the United States, we already have a pharmaceutical formulation of it used with some antibiotics. This is because it reduces the urinary excretion of these drugs. There are also phase 3 clinical studies of probenecid for heart diseases.”
Inhibition of efflux transporters as a therapeutic strategy
At LUTED Lab, the idea of working with probenecid arose from a project that studied efflux transporters. These transporters are mechanisms that expel drugs out of the cell, preventing them from exerting their therapeutic effects. They are highly abundant in some types of cancer and therefore contribute to resistance to chemotherapy.
Probenecid is a relatively weak inhibitor of these transporters. In experiments using lower urinary tract tissues from pigs, rodents, and humans, researchers observed that the drug was able to interfere with these pathways.
This is a pioneering line of research, as highlighted by Prof. Fabiola: “So far, we do not have any studies on probenecid in the urological field. There are studies on its actions in the cardiovascular system, in antibiotic pharmacokinetics, and in alcoholism, where it may act on the Central Nervous System, reducing the desire to drink.”
Dr. Guilherme’s research also investigates the association of probenecid with tadalafil, a drug used to treat erectile dysfunction and benign prostatic hyperplasia. Probenecid has already shown beneficial effects when used in combination with other drugs, such as antibiotics.
Prof. Fabiola explains the advantage of this approach: “When we combine probenecid with other drugs used in the clinic, we observe a strong potentiation of their effects. This allows the use of lower doses and, consequently, fewer adverse effects.”
Young talent highlighted in Brazilian pharmacology
The group’s research has already been gaining recognition. Mariana’s master’s project was nominated for the José Ribeiro do Valle Award, which recognizes young talents in Brazilian pharmacology. The award took place during the 57th Congress of the Brazilian Society of Pharmacology and Experimental Therapeutics (SBFTE), in São Paulo, in October 2025. Mariana was awarded third place.
She shares her experience: “I felt extremely happy and fulfilled to be nominated for such an important award in my field. I have always wanted to work on something that could benefit people. But during graduate school, we become so immersed in the routine of experiments, analyses, and deadlines that we end up forgetting why we are on this path. When the nomination came, it was almost like a reminder. As if someone were saying, ‘hey, this is why you are here, doing something amazing.’ It was a moment of great pride for me and for our research group.”
New molecular targets to understand prostate growth
In addition to the repurposing of probenecid, the laboratory continues to investigate the role of efflux transporters. In this line of research, postdoctoral researcher Dr. Gabriela Reolon (FAPESP fellow, grant no. 22/11621-5) is involved.
She explains: “My main research project aims to evaluate the function of efflux transporters types 4 and 5 in benign prostatic hyperplasia, known as MRP4 and MRP5. More specifically, I investigate the contribution of these cyclic nucleotide transporters to both smooth muscle hyperactivity and cell proliferation processes, using human prostate tissue and human cell lines.”
In other words, she studies two specific types of these transporters, focusing on the transport of cyclic nucleotides, molecules that are essential for cellular communication. If a cell expresses many efflux transporters, it will consequently expel large amounts of these nucleotides, which may interfere with several intra- and extracellular processes.
To illustrate this, we can use a metaphor: imagine a bar with security guards responsible for removing people who are causing trouble. In this case, the bar represents the cell, the guards represent the efflux transporters, and the people represent the cyclic nucleotides. Now imagine that this bar hires too many guards and trains them to remove people indiscriminately. What would be the consequences for the functioning of the establishment?
This is exactly what Dr. Gabriela investigates. First, whether there is an increase in the expression of these transporters in prostatic hyperplasia. And second, how the increased efflux of cyclic nucleotides contributes to muscle hyperactivity and cell proliferation, two key factors in prostate enlargement.
How DNA editing helps us understand diseases
During her postdoctoral studies, Dr. Gabriela completed a research internship at the University of Birmingham through the BEPE program (Research Internship Abroad Fellowship) funded by FAPESP (grant no. 24/00216-8). Under the supervision of Prof. Dr. Davide Calebiro, she worked with techniques that were new to her career, such as cell transfection and plasmid design. These are genetic engineering techniques that allow DNA to be edited and introduced into target cells.
Using these approaches, Dr. Gabriela was able to induce high expression of the efflux transporters she studies (MRP4 and MRP5), recreating in the laboratory the scenario investigated in prostatic hyperplasia.
She describes her experience in the United Kingdom: “In addition to the complexity of the project itself, everything was quite challenging: being in a new country, in a new laboratory, and working with techniques different from those I used in Brazil. Still, it was a very positive experience that contributed significantly to my professional and personal development.”
Translational research and the use of human tissues
LUTED Lab works with both animal models and cell culture, as well as human tissues. The use of human samples is part of what is known as translational research, which aims to transform basic science knowledge into practical applications that benefit patients. For this reason, the group collaborates with physicians, such as pathologist Dr. Guilherme Rossi Assis de Mendonça and urologists Dr. Adriano Fregonesi and Dr. Cristiano Mendes Gomes.
Prof. Fabiola explains: “Clinicians are essential both for translation and as providers of human tissue. We work with corpus cavernosum from patients who have undergone gender-affirming surgery, prostate tissue from patients who underwent prostatectomy, and bladder tissue from patients who required surgical procedures, such as in the case of diabetics. Without these professionals, we would not have access to these materials.”
Despite its advantages, working with human tissue presents challenges. The first is approval by the Research Ethics Committee, which can take 60 to 90 days. In addition, there are logistical difficulties in obtaining the tissues: appropriate solutions must be prepared on the day of surgery, and students must be available at non-conventional working hours. In some cases, the use of high-intensity lasers during surgery can damage the tissues, making them unsuitable for laboratory use.
Even so, translational research is one of the most motivating areas for the group. Dr. Gabriela comments: “What surprises and excites me the most is seeing translational research bringing findings from animal models to humans. This shows that we are on the right track and that these findings may have real impact.” Mariana adds: “That’s when research becomes a bit more real. You start to see that what is happening in the lab can actually have clinical relevance.”
Although the use of human tissues is essential, animal models cannot be fully replaced. Prof. Fabiola explains: “If we had access to human samples every day, we would not work with animals. For example, this week three surgeries were scheduled and all three were canceled. In addition, the material we receive is often very limited.”
From researcher training to societal impact
Dr. Gabriela has been working with Prof. Fabiola since 2017 and is currently the longest-standing researcher at LUTED Lab. Reflecting on her journey, she says: “Being in Prof. Fabiola’s lab is very positive. She is open to teaching, collaboration, and constant support. Everyone here is always willing to help. Over this time, I have developed a lot as a researcher and built a strong academic background, as well as great friendships.”
The work developed at LUTED Lab exemplifies how scientific research can go beyond the laboratory, connecting basic knowledge to clinical applications. The lab investigates drug repurposing and deepens the understanding of the mechanisms involved in urological diseases. In this way, the group contributes to the development of more accessible and effective therapies. Between discovery and innovation, LUTED Lab paves the way for science to become a tangible benefit for society.
This article was produced with the support of the São Paulo Research Foundation (FAPESP), Brazil. Grant No. 25/17158-3. The opinions, hypotheses, conclusions, or recommendations expressed in this material are the responsibility of the author(s) and do not necessarily reflect the views of FAPESP.
Further reading:
Lower urinary tract symptoms and erectile dysfunction (DOI: 10.1016/j.semerg.2015.07.005)
Drug repurposing (DOI: 10.21577/1984-6835.20250006)
Probenecid as an inhibitor of pannexin-1 channels (DOI: 10.1152/ajpcell.00227.2008)
Tadalafil in the treatment of benign prostatic hyperplasia (DOI: 10.1080/14656566.2019.1589452)
MRP4 and MRP5 transporters in prostatic hyperplasia (DOI: 10.1007/s00345-025-05929-2)
Written by:
Mia Schezaro Ramos
Pharmacist. Ph.D. in Pharmacology. Science journalist, illustrator, trans, Nintendo enthusiast, K-pop fan, and dependent on physical exercise to stay sane.