Rising Stars: New Faculty Members Lead to New Discoveries at UCSF

Sandy Wong, MD  

Recruited to UCSF from Tufts Medical Center in Boston, Sandy Wong, MD is an integral part of the Grand MMTI team, where 80 percent of her patients have multiple myeloma. She specializes in studying light-chain amyloidosis, an extremely rare blood plasma cell cancer that affects approximately 4,000 new patients each year in the US. An expert on plasma cell diseases, Dr. Wong is intent on streamlining the diagnosis and treatment of light-chain amyloidosis and multiple myeloma. 

 

Unlike multiple myeloma, light-chain amyloidosis can be difficult to diagnose because the symptoms tend to mimic common disorders. For instance, many people in the US appear to have congestive heart failure or renal failure before being diagnosed with amyloidosis. Because the heart and kidneys are the most commonly affected organs, the diagnosis is often missed or not made until late in the disease when patients experience multiple-organ failure. 

 

"We work really closely together in the Grand MMTI, both clinically and in terms of translational research, to find new strategies to help our patients," Dr. Wong says. "One of those strategies is to prolong survival rates of patients with light-chain amyloidosis. There are varying stages of the disease, with a typical prognosis of six months for those patients with late-stage cardiac disease." 

 

Fortunately, Dr. Wong and her team members are working on a serum-free light-chain assay, an imaging technique that could assist in diagnosis. In patients with these plasma cell diseases, the malignant plasma cells overproduce a type of antibody, the components of which can be measured by this assay. There are fragments within the antibodies that act as surrogates for measuring the disease in the body and can assist in diagnosing the patient's stage. 

 

"The serum-free light chain is considered part of a new standard of care, so we use this routinely at diagnosis and as the patients go through chemotherapy" Dr. Wong says. "We check it regularly to monitor amyloid disease burden - the deposits in the body - over time and use it to see if we can predict organ response and therefore survival. Early diagnosis is key to a patient's survival." 

 

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Arun Wiita, MD, PhD  

In 2016, Arun Wiita, MD, PhD, received a National Institutes of Health New Innovator grant for pushing the boundaries of mass spectrometry technology to track the kinetics of protein-folding across thousands of different proteins in cells in near-real time. "There is a genetic basis for multiple myeloma that can be linked to progression and prognosis," Dr. Wiita says. "Our research aims to better understand the genetics of disease and it influences cancer growth as mediated by proteins." 

 

The immune system plays a central role in the prevention and treatment of multiple myeloma, a disease that Dr. Wiita researches as part of the Grand MMTI team. Early on, the immune system acts like a sentinel, detecting and destroying precancerous plasma cells before they can become malignant. However, if these precancerous cells evade the immune system and advance to full-blown disease, we now have therapies that can engage the immune system to again cause it to attack myeloma in those patients who have become resistant to current immunotherapies. 

 

"We've had a lot of great partnerships with local biotech companies that want to develop new myeloma therapeutics," Dr. Wiita says. "Often they'll come to the UCSF Grand MMTI team to collaborate and demonstrate efficacy of their exciting molecule in preclinical models of myeloma. Together, we determine whether we can make an investigational new drug application and actually put a new molecule in trials for UCSF patients." 

 

Dr. Wiita's lab uses mass-spectrometry technology in tandem with in vitro and in vivo mouse models to ascertain the efficacy of new drugs and their ability to locate and identify immunotherapy targets in the form of cell surface proteins. Previously, these targets on the cell surface were invisible with standard DNA or RNA sequencing. But now they can specifically isolate those proteins at the cell surface and study them through the use of mass spectrometry. 

 

Dr. Wiita and the Grand MMTI team are going one step further and creating models of resistance to known immunotherapies for myeloma. In this way, they hope to understand what changes occur at the cell surface and then use this model to explore how to overcome resistance. 

 

"Today we're trying to make models of resistance to daratumumab, an effective immunotherapy for myeloma," he says. "Even if patients become resistant to that one drug, we can predict how their disease will react to a different immunotherapy and target that after resistance occurs. In that way, we'll always be one step ahead of myeloma." 

Taking a STAND against prostate cancer 

 

"A particular focus of mine was to set up a multidisciplinary clinic for men receiving hormone therapy," Dr. Aggarwal says. "At the STAND Clinic, we are finding ways to improve upon ADT treatment and the side effects it can cause."