Alam Lab

The Alam Lab, led by Dr. Hasan B. Alam, is researching novel strategies to improve survival of lethal injuries.

Current Research in the Alam Lab

The Alam Lab, led by Dr. Hasan B. Alam, focuses on two large and daunting problems facing both civilian and uniformed populations: traumatic injury and severe infection, or sepsis, which often emerges in the days, weeks or months following these life-threatening injuries. Our goal is to minimize loss of life and disability in trauma survivors. In alignment with the National Academies of Science, Engineering and Medicine (NASEM) report, and the goals of the American College of Surgeons Committee on Trauma, we aim to achieve zero preventable deaths. Reality is, the approaches to treating traumatic injuries – including resuscitation and hemorrhage control – as well as sepsis and septic shock have not changed significantly in decades. This fact drives us to find new and innovative strategies to shape the "next frontier" of trauma research and care. A major area of interest for us is in improving care in the immediate post injury phase, especially when delivered in austere environments, where patients lack access to medical facilities or specialized treatment.

Our work spans basic bench research on the function of genes, proteins and cells to pre-clinical studies and translation to bedside clinical care. We are proud of our strong and sustained funding record over the past two decades from organizations such as:

  • National Institutes of Health
  • U.S. Army
  • U.S. Navy
  • Defense Advanced Research Projects Agency, or DARPA

Resulting discoveries are clarifying the mechanisms involved in the body's response to traumatic injury and infection. And they continue to help us identify novel approaches, tools and therapies to help save lives.

For example:

  • A battefield dressing we developed to control heavy bleeding was added to every U.S. Marine's first aid kit.
  • Target proteins we've identified can help clinicians more quickly diagnose infections, which minimize delays in starting life-saving therapies and avoid overtreatment.
  • Research into cell preserving drugs and their optimal dosages have allowed us to activate the body's innate survival mechanisms and reduce the risk of systemic infection and organ damage. One of these agents is now going through clinical trials.
  • We have identified novel treatments for severe traumatic brain injury that can attenuate the magnitude of neuronal damage and speed up the recovery process.
  • Refinements in global preservation strategies, such as induced hypothermia, have led to the start of a federally funded clinical trial of profound hypothermia for patients in traumatic arrest.

The Problem

Injuries are the number one cause of death for people under the age of 44, resulting in a higher mortality rate than all other causes of death combined. The costs are staggering — over $600 billion annually in the United States alone. This cost includes not only medical care but also lost productivity when otherwise active, healthy people become disabled. Globally, injuries account for 10% of all deaths. Millions more individuals survive the initial injury but suffer lifelong harm and disability.

Improvements in trauma care in recent years, unfortunately, have not led to corresponding improvements in mortality. Recent research has shown that most deaths, as in the past, still take place within the first hours after injury. The patients that survive the initial injuries, often succumb to complications, such as lethal infections during the prolonged recovery period. The two major causes of death for these patients are blood loss and severe brain injuries in civilians and soldiers alike. Hemorrhage is about 50% of all deaths in both civilian and battlefield.  ~90% of all deaths in the military occur before reaching higher levels of care. These sad statistics point to the need for improved approaches to hemorrhage control and resuscitation and novel treatments for traumatic brain injury (TBI) — before patients get to the hospital. We need to find new ways to minimize damage and bridge the dangerous gap between injury and definitive medical care.

The Approach

Our lab is looking at a variety of epigenetic and precision medicine "pro-survival" approaches. Our goal is to develop novel treatment strategies that can be used in the austere battlefield conditions to keep the injured alive, and to minimize organ damage and disability during prolonged evacuation to higher echelons of care. Outcomes after traumatic injury vary widely, even when patients are matched by type and severity of injury and many other variables.

Genetic differences don't explain this diversity of outcomes. Our lab found that the expression of about 7% of genes, and the downstream pathways they regulate, are affected by hemorrhage and subsequent resuscitation. This gives us targets to investigate to turn on patients' innate pro-survival genes and activate cell-preserving proteins. More specifically, one key pathway involves a family of enzymes, histone deacetylases (HDACs), that — along and ideally in balance with histone acetyltransferases (HATs) — help regulate how genes are expressed or silenced  by changing the acetylation patterns on nuclear proteins called histones. Even more importantly, modulation of acetylation status of cytoplasmic proteins can immediately, and reversibly alter their functions.  So far, more than 3000 such proteins have been identified that control nearly all key cellular functions.  By administering pharmacologic agents targeting these enzymes, we can alter the acetylation status of cellular proteins, which in turn can activate numerous pro-survival and anti-inflammatory pathways- i.e. create a “pro-survival” phenotype.

Contributions to Science

Our contributions include:

  • Developing novel treatments for hemorrhage control
  • Identifying the consequences of conventional (crystalloid) resuscitation fluids and clarifying the mechanisms involved in activating inflammatory pathways
  • Developing new treatments to mitigate brain damage in traumatic brain injury (TBI)
  • Identifying biomarkers to speed the diagnosis of infection and to monitor progress during TBI treatment
  • Use of hypothermia as a novel technique for surviving lethal injuries, which is now being tested in clinical trials