‘It’s like being able to see a dime on the surface of the moon.’
When physicians observe or hear of symptoms in their patients, they order CT scans, MRIs or other types of imaging analyses to understand the causes.
Clinical imaging, however, does not illuminate the vast machinations of life that occur deeper within, at the Lilliputian level of individual proteins and other molecules. Chain reactions in this tiny domain determine whether good health continues, or diseases begin. To explore how the reactions foster disorder, scientists acquire images with state-of-the-art instruments capable of ultra-high resolution. They employ statistical models to work out molecular structures. The overall analysis yields sites of disease susceptibility that can be targets for drug therapies.
UT Health San Antonio is investing $5 million over the next three years in such a technology, called cryo-electron microscopy, or cryo-EM for short.
“We are essentially molecular photographers,” said Shaun Olsen, PhD, associate professor of biochemistry and structural biology and director of structural biology cores. “Some people take pictures of buildings. We take pictures of proteins and want to see what they look like in three dimensions.”
Cryo-EM visualizes proteins that are extremely difficult to image using other techniques, said Elizabeth Wasmuth, PhD, assistant professor of biochemistry and structural biology.
Cryo-EM is complementary to existing structural biology technologies at UT Health San Antonio. X-ray crystallography, for example, exposes a protein crystal to X-rays, diffracting the X-ray beam in directions according to the protein’s structure. Nuclear magnetic resonance (NMR) spectroscopy, meanwhile, demonstrates behavior of an atom nucleus when it is placed in a powerful magnetic field. Experts can infer structure from the behavior they observe.
“We look at molecules in levels of detail that are unparalleled,” Wasmuth said. “So, basically, it’s like being able to see a dime on the surface of the moon. This is the level of resolution that the techniques and tools of structural biology allow us to see about molecules inside cells, inside our bodies. Cryo-EM adds a powerful new dimension to our other methods.”
Some protein targets are too small to be visualized by existing techniques or have flexible, wiggly regions that impede the crystal formation, Wasmuth said. Cryo-EM flash-freezes proteins on thin layers of ice within milliseconds and barrages them with electron beams, generating biologically useful information.
“Having a cryo-EM system will allow us to observe drug targets that couldn’t be visualized by the other methods,” Wasmuth said. “The second week the cryo-EM facility became functional, we were able to solve the structure of a complex of proteins involved in DNA damage repair at impressively high resolution. I am confident that this tool is going to transform structural biology research here like we haven’t seen before.”
Much like the space telescopes in Chile, Hawaii and West Texas are indispensable shared resources for astronomers, cryo-EMs are invaluable shared resources for structural biologists.
“We have to remain competitive, and this is a question that a lot of academic medical centers are trying to decide right now: Where will we fit within the research environment?” said Jennifer Sharpe Potter, PhD, vice president for research. “This acquisition reflects our commitment to making San Antonio a biomedical hub for the United States and the world. The types of visualizations and the questions that this technology advances are investments in the long-term improvement of human health.”
Robotic kidney cancer surgery shows desirable outcomes in study
Kidney cancer is not always confined to the kidney. In advanced cases, this cancer invades the body’s biggest vein, the inferior vena cava, which carries blood out of the kidneys back to the heart. Via the IVC, cancer may infiltrate the liver and heart.
The Mays Cancer Center at UT Health San Antonio is one of the high-volume centers in the U.S. with surgical expertise in treating this serious problem.
In a study featured on the cover of the Journal of Urology, researchers from the Mays Cancer Center and the Department of Urology at UT Health San Antonio show that robotic IVC thrombectomy — the removal of cancer from the inferior vena cava — is not inferior to standard open IVC thrombectomy and is a highly safe and effective alternative approach. The affected kidney is removed along with the tumor during surgery, which is performed at UT Health San Antonio’s clinical partner, University Hospital.
Harshit Garg, MD, urologic oncology fellow in the Department of Urology, is first author of the study, and Dharam Kaushik, MD, urologic oncology fellowship program director, is the senior author.
The open surgery requires an incision that begins 2 inches below the ribcage and extends downward on both sides of the ribcage.
“It looks like an inverted V,” Kaushik said. Next, organs that surround the IVC, such as the liver, are mobilized, and the IVC is clamped above and below the cancer. In this way, surgeons gain control of the inferior vena cava for cancer resection.
“Open surgery has an excellent success rate, and most cases are performed in this manner,” Kaushik said. “But now, with the robotic approach, we can achieve similar results with smaller incisions. Therefore, we need to study the implications of utilizing this newer approach.”
The study is a systematic review and meta-analysis of data from 28 studies that enrolled 1,375 patients at different medical centers. Of these patients, 439 had robotic IVC thrombectomy and 936 had open surgery. Kaushik and his team collaborated with Memorial Sloan Kettering Cancer Center, New York; Cedars-Sinai Medical Center, Los Angeles; and the University of Washington, Seattle, to perform this study.
The results are encouraging, finding:
- Fewer blood transfusions: 18% of robotic patients required transfusions compared to 64% of open patients.
- Fewer complications: 14.5% of robotic patients experienced complications such as bleeding compared to 36.7% of open thrombectomy patients.
These large, technically challenging surgeries last eight to 10 hours and involve a multidisciplinary team of vascular surgeons, cardiac surgeons, transplant surgeons and urologic oncology surgeons, Kaushik said.
This is the largest study to analyze the outcomes of robotic versus open IVC thrombectomy, Kaushik said. While open surgery remains the gold standard for surgery, the study shows the robotic variation could be a good option for certain patients, he added.
“Optimal candidacy for a robotic surgery should be based on a surgeon’s robotic expertise, the extent and burden of the tumor, and the patient’s comorbid conditions,” Kaushik said.