Dr. Sacchettini first came to Texas A&M in 1995 and opened the laboratory in the biochemistry department. Since that time, the lab has greatly expanded in size as well scope and techniques. The lab strives to be on the cutting edge of technology and to supply its members with all the possible resources to accomplish their goals.
We are working on several projects, using structural biology to answer questions about different diseases that affect human health. Please click on the links below for more information on the work being done in this lab.
What is it? Tuberculosis (TB) is an infectious disease caused by a bacterium. Approximately two billion people, one third of the Earth's population, are infected with TB, mostly in the third world although there has been a resurgence in the first world due largely to the spread of HIV/AIDS. There are approximately 8.5 million new active cases and 2 million deaths annually from TB. Most of these deaths are preventable with antibiotic treatment. T
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Causes of TB
The causative agent of tuberculosis is bacteria from the Mycobacterium species, mostly Mycobacterium tuberculosis, although other mycobacteria such as M. bovis can also cause TB disease in humans. The bacteria is spread through the air when an infected person coughs or sneezes. M. tuberculosis usually infects the lungs (pulmonary TB) but it may also infect the lymphatic system, circulatory system, the skin and other organs (systemic TB). By far the majority of people infected with mycobacterium do not develop symptoms and do not spread the disease to others, this is known as latent TB infection. In latent TB infection a small amount of TB bacteria remains in the body but is kept in check by the immune system, unable to cause disease. If, however, the immune system is comprimized, such as through serious illness, it is possible that the latent infection can become an active TB infection.
Active TB infection can arise immediately after being infected with TB bacteria or it may develop from an existing latent infection. It is during active TB infection that it is possible to spread the disease to others and when symptoms are presented. Symptoms include coughing, weakness, weight loss, fever, chills and night sweats.
Current treatment
Both active and latent TB infection are treated with antibiotics. There are currently several antibiotics in use to treat TB infection, divided into the categories of first line drugs, the first drugs used to treat TB infection, and second line drugs, used when the first line drugs are not effective in eradicating the bacterium. The table below lists some of these drugs.
First line drugs
Second line drugs
Isoniazide
Ofloxacin
Rifampicin
Ciprofloxacin
Pyrazinamide
Sparfloxacin
Ethambutol
Clarithromycin
Streptomycin
Thiocetazone
Ethionamide
Cycloserine
In over 95% of cases, TB disease is treatable using the first line drugs alone over a period of six to nine months. However, due to poor health care practices, two new strains of TB are emerging that are resistant to antibiotics, multidrug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB).
MDR-TB is defined as TB that is resistant to the two most commonly used anti-TB antibiotics, isoniazid and rifampicin. A recent survery by the WHO has found that MDR-TB represents approximately 5% of all new TB cases worldwide, and represents over 15% of new cases in some countries. This is an increase from an earlier WHO survery, highlighting the need for new drugs to fight TB infection.
XDR-TB is MDR-TB that is also resistant to three or more of the existing six classes of second line anti-TB drugs, making it virtually untreatable. It also has a high mortality rate compared to normal TB. The WHO reports that XDR-TB has been identified all over the world but it is most commonly found in the former Soviet Union and Asia. In the U.S., 4% of MDR-TB cases met the criteria for XDR-TB.
The Sacchettini lab is part of a consortium of labs that are researching TB and looking for new ways to combat this bacterium. Click the link below to find out more:
Malaria is a widespread vector-borne disease caused by parasites in the Plasmodium family (specifically Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae) and transmitted by the bite of an infected female Anopheles mosquito. Each year between 300 and 500 million people are infected and more than one million people die, most of them children and pregnant women. Malaria is associated with tropical and subtropical climates because the warm temperature allows the Anopheles mosquito to grow year round.
Causes of malaria
A female Anopheles mosquito ingests a blood meal from an infected person which contains gametes. Fertilization occurs in the mosquito’s gut and sporozoites develop which are then injected into the next host when the mosquito feeds. The sporozoites travel to the new host’s liver and develop into merozoites which then penetrate red blood cells and develop into gametes which are taken up by another mosquito.
Treatment
There are no vaccines against malaria. Malaria control is divided into two categories, prevention and treatment. When in a high risk area for malaria people are encouraged to use insect repellent containing DEET and to wear long sleeves and pants to avoid being bitten by mosquitos. Sleeping under a treated sleep net also prevents being bitten and being infected. Once a person is infected there are several drugs that can be used that target the parasite in the blood including chloroquine, sulfadoxine-pyrimethamine, mefloquine, atovaquone-proguanil, quinine, and doxycycline. However, widespread use of these drugs and poor health care management has resulted in the development of resistance especially against chloroquine. Additionally the Anopheles mosquito has developed resistance to many of the commonly used insecticides, making prevention efforts more difficult.
Economic Impact
The economic impact of malaria on poor countries and individuals is enormous, with some highly affected countries spending significant portions of public health care funding on malaria treatment. Individuals with malaria not only pay significant portions of their personal income on treatment but also suffer decreased attendance at work and schools, perpetuating a cycle of poverty.
Non-Hodgkin's lymphoma (NHL) is a cancer that originates in lymphatic tissues. Last year, 20,210 people died from NHL in the US. Standard treatment for an aggressive type of NHL consists of IV infusion with a chemotherapy cocktail known as R-CHOP. R-CHOP therapy results in complete remission in 75-80% of people and 50-60% of those remain free of this deadly disease for 3-5 years. Unfortunately a significant number experience early treatment failure (they don’t respond), partial response (they respond but their disease does not go away), or relapse (their disease disappears but recurs several years after treatment is stopped). Patients with recurrence who initially respond to R-CHOP but then develop new tumors appear to respond less optimally when a new course of R-CHOP is begun and many eventually die. Therefore treatment of NHL is, like many other cancers, hampered by resistance to our drugs.
We have created a novel platform to develop drugs that combat drug-resistant cancers. Using this platform we hope to develop a drug that will improve cure rates by reducing drug-resistance of cancer cells to current combinatorial drug therapies and lowering the toxicity of current treatments.
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