2019 Research Project Summaries

MEDICAL STUDENT SUMMER FELLOWSHIPS

Nyle Almeida, BS

 Synaptogenic Glioma Cell Enrichment in High Connectivity Regions of Adult Glioma

Previous research has shown that gliomas disrupt communication between nerve cells in the brain and cause neurocognitive deficitsThe loss of brain function. Recently, Dr. Shawn L. Hervey-Jumper of the UCSF Brain Tumor Research Center identified glioma cells that have the ability to make connections with healthy neurons, called synaptogenic glioma (SG) cells.

  • Synaptogenic glioma (SG) cells: a specific type of cell within a glioma tumor that helps to establish connections between nerve cells.

Preliminary data from the Hervey-Jumper lab indicates that the presence of SG cells in a tumor may increase a patient’s chances of recovering from tumor-induced aphasiaThe inability to understand or produce speech.

In my previous work in the Hervey-Jumper lab, I used cutting-edge neuroimaging technology to measure neuronal activity and found glioma subtypes support neuronal communication in different ways. In my ABTA Medical Student Summer Fellowship project, I will look for genes that are important for glioma-neuron communication using samples from glioma patients to identify the SG cells. I will then:

  1. Investigate whether SG cells divide more frequently than other glioma cells, causing faster tumor growth.
  2. Verify that SG cells can enhance communication among hippocampal neuronsBrain cells that are important for memory, learning, and emotion using patient cells in culture.

This study is the first of its kind to examine the impact of synaptogenic glioma cells on functional communication in the brain.


Sakibul Huq, BS

Identification of EZH2 and elf4E as New Therapeutic Targets in Chordoma

Chordoma is a rare, aggressive cancer of the skull base and spine that often goes undetected until it has reached an advanced stage. Despite extensive efforts from the scientific community, little is known about the underlying biology of chordoma, and there are currently no FDA-approved drugs to treat patients. Consequently, management of this cancer is notoriously challenging.

Recent research suggests that EZH2 and eIF4E, proteinsMolecules that perform the functions of genes such as to stimulate growth or migration involved in central processes in many cancers, may also play important roles in chordoma.

We hypothesize:

  1. The amount of EZH2 and eIF4E in a patient’s chordoma correlates with patient prognosis.
  2. Targeting EZH2 and eIF4E with drugs may provide a strong therapeutic response in chordoma.

We will test our hypotheses through three specific aims:

  1. Evaluate the effects of blocking EZH2 and eIF4E in human chordoma cells in cultureCell culture refers to the removal of cells from a human, animal or plant to be further studied in a favorable controlled conditions in a laboratory.
  2. Measure the impact of blocking EZH2 and eIF4E on chordoma tumors grown in mice.
  3. Determine whether the amount of EZH2 and elF4E in each patient’s tumor correlates with their overall prognosis.

Our goal is to provide evidence for new treatment options for patients with this rare and debilitating cancer.


Rushikesh Joshi, BS

Identifying Mediators of Perivascular Invasion in Glioblastoma

The poor prognosis of glioblastoma (GBM) is largely due to GBM cells spreading into healthy brain tissue, which makes complete surgical removal impossible. Invasion inevitably leads to tumor recurrence, typically within two centimeters of the initial diagnosis location. Within the primary tumor, the blood brain barrier (BBB)A border that allows some materials to cross over, but protects the brain from foreign substances in the blood that may injure the brain. is typically weaker, allowing the tumor to be more accessible to systemic chemotherapyChemotherapy that reaches the tumor through the blood stream, such as oral or i.v. chemotherapy..

However, when tumor cells invade other parts of the brain (away from the main tumor site), it becomes harder to target these cells with chemotherapy because they have invaded regions of the brain where the BBB is still intact, preventing drugs from getting through. Because of this, tumor cells have free range to invade critical areas of the brain and disrupt essential functions. Furthermore, additional surgeries exert equally devastating effects on quality of life, inhibiting subsequent treatment efforts.

  • Integrins: Molecules on the surface of cells that are responsible for attaching cells to surrounding extracellularOutside the cell materials (such as blood vessels). They also communicate signals between the environment and the inside of the cell.

Using biopsies taken from various regions of the same tumor (at both the primary site and tissue the tumor cells have invaded), the Aghi lab has found greater amounts of specific integrins on the periphery where tumors are invasive. Because integrins connect cells to blood vessels, my summer project will investigate the hypothesis:

As cells move away from the tumor core, they react to cues in the environment around them that cause a transition towards perivascular invasion, which can be blocked with targeted therapy.

I will investigate this hypothesis by blocking integrin signals and by studying perivascular invasion using a 3D cell culture modelAn artificial environment where cells can grow and interact with their surroundings in all directions. 3D culture allows the cells to grow more similarly to how they would grow in the body.. In seeking a better understanding of the various elements that make GBM so invasive, we hope to find specific aspects of the tumor, such as integrins, to target with drugs to suppress malignant invasion and ultimately improve patient outcomes.


Shoeb Lallani, BS

Defining a Role for the GCH1/BH4 pathway in Brain Tumor Therapeutic Resistance

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Even after surgery, radiation and chemotherapy, the tumor typically grows back rapidly, resulting in a dismal patient prognosis.

The presence of cancer stem cells – cancer cells that have properties of normal stem (immature) cells, specifically the ability to generate any type of cancer cell found in a tumor sample – in GBM is one of the many reasons this tumor type is difficult to treat because cancer stem cells are able to survive chemotherapy and radiation treatment. Additionally, there are currently minimal ways to predict whether a brain tumor will or will not respond to specific treatments. This makes creating the best treatment plan for individual patients extremely difficult. With this project, we hope to:

  1. Determine whether specific biomarkers can indicate which patients will have better or worse outcome
  2. Better understand the ways that brain tumor cells survive and cause tumor recurrence and block the molecules involved with specific drugs to see if they kill tumor cells.

Learning more about both of these will help in designing the best treatments for individual patients.


Melanie Schweitzer, BS

Notch-Targeted Therapy for Choroid Plexus Carcinoma

Choroid plexus (CP) tumors are primary brain tumors predominantly found in young children and infants. There are two types of CP tumors:

  • CP papilloma: A benign type of choroid plexus that has excellent prognosis when removed though surgery
  • CP carcinoma: A highly lethal type of choroid plexus that is poorly understood and has few treatment options available

In order to study CP carcinomas, we created genetic mouse models that develop CP papillomas and CP carcinoma-like tumors, which have helped us to define and understand characteristics of the tumor cells.  In this application, we will further develop the CP carcinoma mouse model to:

  1. Determine if the tumor characteristics we discovered are a weakness in CP tumors that can be targeted with therapy
  2. Test a novel targeted inhibitorA drug that specifically blocks on or a few cancer-driving signals in cells in our model to block CP carcinoma growth.

Successful completion of these studies will help to propel these findings into clinical trials for patients with CP carcinoma.

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