Soumil Sharma
Pentavax: Pentraxin proteins with Dengue Virus Immunoreactivity
Mentors: Dr. Scott Willett and Kevin Gerbrick (Baruch S. Blumberg Institute)
- 4th Place, Regeneron International Science and Engineering Fair (ISEF)
- Finalist, Regeneron International Science and Engineering Fair (ISEF)
- Silver Medal, Senior Fair, Delaware Valley Science Fair (DVSF)
2nd best project for any senior in tri-state region! - 1st Place, Delaware Valley Science Fair (DVSF)
Best Microbiology project for any senior in tri-state region! - Chromatography Forum of Delaware Valley (CFDV) Award
- 2nd Place, Bucks County Science Research Competition (BCSRC)
- 1st Award (Perfect Score), Pennsylvania Junior Academy of Science (PJAS)
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
The dengue virus (DENV) affects over 400 million people each year and can lead to organ failure and death. Until 2024, there was only one current vaccine option for dengue; however, studies have shown that this vaccine has actually led to worsened symptoms for patients, because it is ineffective at building immunity to all four serotypes of the virus. My research is focused on developing particles that could be used in a new dengue vaccine, that is effective against all four serotypes of DENV. This year, three Pentraxin proteins were developed with different conserved DENV NS1 peptides as potential candidates for a new dengue vaccine. The proteins, named “Pentavaxes”, were produced through mammalian cell transfection and purified using PE chromatography. UV scans determined that protein was present, and protein gels determined that the Pentavaxes had been produced at their correct molecular weight. Western Blots will be run soon to determine if the Pentraxins can bind to DENV antibodies, indicating immunoreactivity. Additionally, new Pentavax designs are being developed with combinations of multiple DENV peptides as a possible method for achieving multivalency.
Soumil, a graduate of CB East, will attend University of Pennsylvania in the fall, where he plans to study biophysics or Neuroscience on the pre-med track. Soumil is a National Merit Finalist who won this year's Cross Culture Scholarship.
Prisha Parmar
Bioengineering an Antibody Drug Conjugate for Uveal Melanoma
Mentors: Dr. Scott Willett and Kevin Gerbrick (Baruch S. Blumberg Institute)
- Finalist, Regeneron International Science and Engineering Fair (ISEF)
- Bronze Medal, Senior Fair, Delaware Valley Science Fair (DVSF)
3rd best project for any senior in tri-state region! - 1st Place, Delaware Valley Science Fair (DVSF)
Best Engineering project for any senior in tri-state region! - Society of Women Engineers - Philadelphia Section
- 1st Place, Bucks County Science Research Competition (BCSRC)
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
Uveal melanoma is the cancer of the melanin producing cells inside the eye. Among patients with this disease, approximately 50% develop metastatic disease, cancer cells spread to other parts of the body. Despite there currently being two FDA approved therapies to treat this disease, approximately 40% of patients unfortunately pass away 10-15 years after initial diagnosis. My research focuses on using Antibody Drug Conjugates (ADCs) to treat this disease as well as studying potential improvements to the ADC structure that may improve its effectiveness. ADCs consist of an antibody, a protein produced by the immune system to recognize and neutralize foreign substances such as bacteria and viruses, and a cytotoxic drug, such as a chemotherapeutic drug. Together, they can recognize and kill cancer cells. By utilizing and improving this system, a potential therapy can be created to target uveal melanoma more effectively.
Prisha, a CB South graduate, will attend Case Western Reserve University, where she will study biology. Prisha aspires to become a physician.
Sudhir Yelamarthy
Exploring Novel RAD52 Inhibitors using Bioisosteric Modification of Known Inhibitors, Year 2
Mentors: Dr. Gideon Tolufashe (Baruch S. Blumberg Institute)
- 1st Place, Delaware Valley Science Fair (DVSF)
Best Chemistry project for any senior in tri-state region! - 1st Place, Bucks County Science Research Competition (BCSRC)
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- State Meeting
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
The most common form of genetic breast and ovarian cancer is caused by mutations in the BRCA1/BRCA2 proteins, which repair DNA. 1 in 500 women possess a mutation, of which 50% will develop some form of breast or ovarian cancer. Cancer cells with mutated BRCA1/BRCA2 proteins rely on the RAD52 protein to repair DNA and survive. Inhibiting the RAD52 protein causes cancer cells to die, while causing no adverse effects in healthy cells. 5-Aminoimidazole-4-carboxamide ribonucleotide (ZMP) has been shown to inhibit RAD52 through in-silico and in-vitro testing. However, its drug potential is hindered by its poor permeability. Last year, this was tackled by creating bioisosteres that replaced ZMP’s phosphate group with other functional groups. This year, the best derivative was tested against mutants of RAD52 proteins to understand the compound’s sensitivity and effectivity. Two mutations were created: a natural variant (R70W) that is known to exist and an oligonucleotide-binding (OB) fold mutant (K102A/K133A/K169A/R173A) that is designed to disrupt the binding site of RAD52. Using the Maestro modeling software, the binding interactions between the molecule and proteins were quantified. Finally, the differences between binding to the wild-type and the mutations were analyzed. Overall, the derivative was still able to bind effectively to the mutants, suggesting the ability to inhibit the RAD52 protein and potential as a drug candidate. Further testing in-vitro is required to validate these theoretical results.
Sudhir, a graduate of CB South, will study bioengineering at the University of Pennsylvania.
Anna Ries
Developing a Transdermal Patch for the Beta-Adrenergic Blocking Agent Indicated for the Treatment of Hypertension – Nebivolol
Mentors: Frank Jones, Christine Rittenhouse, Claire Cosfol, Jayne Jones, Brian Jones (Greene Street Pharmaceuticals)
- 1st Place, Delaware Valley Science Fair (DVSF)
Best Chemistry project for any junior in tri-state region! - Chromatography Forum of Delaware Valley (CFDV) Award
- 1st Place, Bucks County Science Research Competition (BCSRC)
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- State Meeting
- Karl F. Overlain Award
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
Hypertension is the leading cause of premature death both nationally and globally, affecting 1 out of every 4 adults worldwide. While current hypertension treatments are effective, medication adherence drops by 50% after just one year. I am developing a transdermal patch to administer nebivolol via a new delivery system to improve medication adherence and treatment effectiveness for hypertension. Nebivolol has a very low oral bioavailability of 12%. When taken orally, only 12% of the original dosage reaches the bloodstream for treatment, while the other 88% is metabolized through first pass metabolism. Bioavailability greatly increases when delivered via transdermal patch as it bypasses first pass metabolism. This allows for less drug to be used in the patch, making it small and cheaper to make as well as purchase. My development process includes conducting a solubility receptor study, making formulations, doing physical testing, and running skin permeation tests. All data is analyzed through Reverse Phase - High Performance Liquid Chromatography. I'm evaluating adhesive properties to identify those that maximize drug delivery, conserving time and resources before testing. In the first round of formulations, I tested acrylic adhesive formulations on human cadaver skin. Key chemical properties of acrylic adhesives include vinyl acetate content, primary functional group, and curing/crosslinking method. I discovered that the drug delivery was most impacted by the compatibility between the adhesive's functional group and the drug. I am now testing acrylic vs. synthetic rubber adhesives, as nebivolol’s lipophilicity may make it more compatible with synthetic rubber.
Anna Ries is a CB West junior who will return to the Biotech Center for a second year of the Program. Anna won the Special Science Research Award at CB West High School and is Director of Social Media for the Student STEM Experiential Learning Foundation (SSELF).
Tamar Ben-Anat
The Effects of a WEE1 Inhibitor in Combination with Trastuzumab Deruxtecan on HER2+ Breast Cancer
Mentors: Dr. Oren Gilad, Molly Hansbarger (Aprea Therapeutics)
- 2nd Place, Delaware Valley Science Fair (DVSF)
- Parenteral Drug Association, Delaware Valley Chapter Award
- 1st Place, Bucks County Science Research Competition (BCSRC)
- 1st Award (Perfect Score), Pennsylvania Junior Academy of Science (PJAS)- State Meeting
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
HER2+ breast cancer makes up roughly 15%-30% of all breast cancer cases. It occurs when the Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed, causing the cancer to grow more rapidly. Trastuzumab Deruxtecan (T-DXd) is a therapeutic currently used in the clinic. T-DXd is an antibody-drug conjugate, meaning it is composed of a monoclonal antibody, which binds to the HER2 receptor, and is linked by a peptide chain to a cytotoxic drug. In the case of T-DXd, the drug is a topoisomerase inhibitor, which induces DNA damage. However, patients can develop resistance to T-DXd, so this research investigates the combination of T-DXd with a WEE1 inhibitor (WEE1i) as a potentially more effective treatment. WEE1 is a protein in the DNA Damage Response pathway that inhibits the CDK1-Cyclin B protein complex, preventing the cell from progressing from the G2 phase into M phase. This provides time for the cells to repair damage. Inhibiting WEE1’s function forces the cell through the cycle, despite the presence of DNA damage, causing the cell to enter mitotic catastrophe. In combination, it is expected that T-DXd would induce DNA damage, and the WEE1i would prevent cells from repairing the damage, ultimately leading to cell death. Testing this combination involves western blotting and conducting MTT assays. The western blot primarily detects levels of γH2AX, a marker of DNA double-stranded breaks, in the cells after being treated with different combinations of the drugs. Preliminary results show elevated γH2AX levels in the combination treatment compared to either agent alone, suggesting enhanced DNA damage and increased effectiveness. The MTT assay assess cell viability, but the results have been inconclusive so far, potentially due to edge effects impacting assay consistency.
Tamar Ben-Anat is a CB South graduate who has been accepted into the 7 year accelerated BS/MD program at Penn State University and Sidney Kimmel Medical College at Thomas Jefferson University.
Devin Yang
Investigating Varying Positions of an ADAR Recruit Element to Increase Efficiency of RNA Editing in Reprogrammable ADAR Sensor (RADARS) Systems
Mentors: Dr. Liudi Tang, Liren Sun (Baruch S. Blumberg Institute)
- 2nd Place, Delaware Valley Science Fair (DVSF)
- 3rd Place, Bucks County Science Research Competition (BCSRC)
- 1st Award (Perfect Score), Pennsylvania Junior Academy of Science (PJAS)- State Meeting
- PA Science Talent Search Award
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
Reprogrammable ADAR Sensors (RADARS) is a novel therapeutic technology that harnesses RNA editing enzymes called ADAR (Adenosine Deaminase Acting on RNA) proteins to perform basic edits on a piece of dsRNA (Double Stranded RNA) formed from a target transcript and an RNA sensor. The ADAR editing enzyme edits Adenosines into Inosines (A->I) on a UAG stop codon in the system. This slight change in dsRNA results in the production of a modifiable downstream protein. While the system has multiple advantages over other therapeutic technologies, such as being reprogrammable and being able to specifically target diseased cells, one of the main drawbacks is its efficiency as the system was designed in 2022. Hence, the goal of my research was to increase the efficiency of the downstream protein production through the use of an ADAR Recruit Element—an additional piece of RNA that makes it more likely for the ADAR protein to bind to the system. To optimize the downstream protein production, I investigated the positioning and quantity of ADAR recruit elements on the RNA sensor. To perform this experiment, I ran multiple transfections, obtaining qualitative results/visualization of transfection efficiency through fluorescence microscopy and quantitative results through a luciferase assay. I was able to find that certain positions of the ADAR recruit element revealed increased downstream protein expression and adding multiple ADAR recruit elements showed minimal to no increase in downstream protein expression. These results have numerous applications in advancing the understanding of RADARS, making it one step closer to becoming a possible therapeutic option for humans in the future.
Devin Yang is a CB East junior who will return to the Biotech Center for his senior year. He plays cello, piano, and clarinet. Devin likes to play and teach Chinese yoyo in his spare time.
Shreejith Krishnamoorthy
Selective Inhibition of MMP-2 for Preventing Decorin Cleavage Linked to Hypermobile Ehlers-Danlos Syndrome
Mentors: Dr. John Kulp, Ryan Ford (Conifer Point Pharmaceuticals), Dr. Scott Willett, Dr. Gideon Tolufashe (Baruch S. Blumberg Institute)
- 3rd Place, Delaware Valley Science Fair (DVSF)
- Johnson and Johnson Award for Biotechnology and Pharmaceutical Research Award
- Parenteral Drug Association, Delaware Valley Chapter Award
- 2nd Place, Bucks County Science Research Competition (BCSRC)
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- State Meeting
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
Hypermobile Ehlers Danlos Syndrome (hEDS), a connective tissue and joint disorder, significantly affects millions of lives. Patients suffer chronic pain and increased susceptibility to injury and disease. This genetic disorder is projected to affect up to 20% of the population in the future, emphasizing the need for targeted therapeutics. Currently, only retroactive pain management and vitamin supplementation are available. In this study, the therapeutic potential of matrix metalloprotease 2 (MMP-2) inhibition was investigated using a hybrid approach, utilizing in-silico and in-vitro validation. This study identified that the expression of MMP-2 was significantly upregulated in hEDS patients. Small molecule inhibitors were proposed to downregulate the enzymatic activity of MMP-2, potentially functioning as effective drug candidates. Selection of candidates was conducted utilizing thermochemical metrics computed in Maestro, an industry-leading drug discovery software. A Kruskal-Wallis H-Test was used to filter ΔGbind scores of inhibitors (p<0.05) against a well-known control inhibitor. Remaining candidates were evaluated manually considering the biological context of the disease. Fifteen top inhibitors were identified for further testing. Experimental validation of the candidates required recombinant MMP-2. MMP-2 was successfully expressed using a novel cleavage mechanism developed to streamline recombinant protein expression. In-vitro inhibition of MMP-2 via small molecule inhibitors reduced the enzymatic activity of MMP-2. The results show that these drug candidates could be a viable therapeutic in treating hEDS by selectively inhibiting MMP-2. Further research will be conducted on synthetic inhibitors for higher potency. Disease models will then be used to establish the effectiveness in-vivo.
Shreejith, a CB South junior, will return to the Biotech Center for his senior year. He has been successful in multiple business-related competitions including FBLA and DECA. Shreejith is a Student STEM Experiential Learning Foundation (SSELF) Leadership Council Member.
Prithvi Krish
Analyzing Exosomal RNA in Liver Specific Exosomes as a Potential Biomarker for HCC
Mentors: Dr. Aejaz Sayeed, Daniel Zezulinski (Baruch S. Blumberg Institute)
- 3rd Place, Delaware Valley Science Fair (DVSF)
- American Association for Cancer Research (AACR) Award
- 2nd Place, Bucks County Science Research Competition (BCSRC)
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- State Meeting
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
Worldwide, liver cancer is the 5th most leading cause for cancer related deaths with a prediction of 1.3 million people to die by 2040. Hepatocellular Carcinoma (HCC), the most common liver cancer type, presents no symptoms, posing a challenge for early detection. The only proven diagnostic approach is an invasive liver biopsy which carries associated risks such as metastasis, complications for elderly patients, and even death in some cases. This research aims to diagnose HCC using a patient’s blood sample (Liquid biopsy) as it is cost-effective/noninvasive as opposed to a Liver biopsy surgery. Liver-specific genes CYP1A2 and Albumin were amplified to analyze if liver-specific Exosomal RNA can be a viable source for HCC biomarkers–genetic indicators of HCC. Exosomal RNA, collected from a membrane-bound vesicle, was targeted as it is more viable and makes a liquid biopsy possible. PCR tests showed the expression of CYP1A2 & Albumin were upregulated in liver-specific exosomes but downregulated in lung-specific exosomes. Moreover, the data signifies the variation in the contents of liver-specific exosomes and cells. Tests conducted on both cancerous and noncancerous-hepatocyte exosomes reveal that CYP1A2 and Albumin are over-expressed in cancerous and under-expressed in noncancerous-hepatocyte exosomes. Data drawn thus far in this research leads to believe that CYP1A2 and Albumin are liver cancer biomarkers and that liver-specific exosomes could be viable sources for HCC biomarkers. This concludes that a simple blood test can be used for HCC diagnosis. Experimentation using patient plasma samples will further validate the potential of CYP1A2 and Albumin as liver cancer biomarkers.
Prithvi, a graduate of CB West, will attend the University of Maryland, where she will study biological sciences. Prithvi will participate in the First-Year Innovation & Research Experience (FIRE).
Ruhin Inder Shaheed
MHC-I/PD-L1 Modulation in Dendritic Cells as a Response to Stimulation Factors
Mentors: Aykan Karabudak, Dr. Hager Mohamed, and Justina Adams (Gylden Pharma)
- Honorable Mention, Bucks County Science Research Competition (BCSRC)
- 1st Award (Perfect Score), Pennsylvania Junior Academy of Science (PJAS)- State Meeting
- Director's Award for Biochemistry
This is the top award given to a high school Biochemistry project. - 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
Infectious diseases are very common, but there is still much more research needed to learn how exactly they affect cells and cellular communication with the immune system. This is important because this knowledge can be used to make more effective immunotherapies to better treat infections. Cells use signalling proteins to communicate with the immune system and previous research has established that the expression of these proteins changes due to infections. This year, I aimed to determine how infections affect the expression of the signalling proteins Major Histocompatibility Complex class I (MHC-I) and Programmed Death Ligand 1 (PD-L1), and their effect on antigen presentation and T-cell interaction. MHC-I is responsible for presenting antigens (foreign proteins found on pathogens) on the surface of Antigen Presenting Cells (APCs) and PD-L1 is associated with deactivating T-cells, which recognize antigens and then begin the immune response. To determine the effects of an infection, I used the mouse dendritic cell line, DC2.4 cells, as APCs, and stimulated them with Lipopolysaccharide (LPS) and Interferon gamma (IFNg), both of which produce inflammatory responses within the cell and simulate an infectious environment. Once I determined an ideal concentration of the two stimuli, I stimulated the cells with that concentration and the antigen SIINFEKL to determine the effect of stimulation on antigen presentation. The results showed that due to stimulation, PD-L1 expression increased, MHC-I expression decreased, and SIINFEKL presentation was negatively affected. Next, I worked on investigating the effect of these observations due to stimulation on the level of T-cell activation by the dendritic cells by introducing the mouse T-cell line, B3Z cells, to the DC2.4 cells. This phase is ongoing and requires further experimentation to determine the effect on T-cell activation.
Ruhin Inder Shaheed is a CB West junior who will return to the Biotech Center for her senior year. Ruhin is Director of Events for the Student STEM Experiential Learning Foundation (SSELF). She is pianist and a black belt in karate.
Athena Man
Single Crystal Growth for Identification of the X-ray Crystal Structure of BDAA
Mentors: Yanming Du, Dr. Yusheng Wu (Baruch S. Blumberg Institute), Dr. Michael Gau (University of Pennsylvania)
- 2nd Place, Delaware Valley Science Fair (DVSF)
- Yale Science and Engineering Association Award
- 3rd Place, Bucks County Science Research Competition (BCSRC)
- 2nd Award, Pennsylvania Junior Academy of Science (PJAS)- State Meeting
- 1st Award, Pennsylvania Junior Academy of Science (PJAS)- Regionals
Yellow Fever Virus (YFV) is a virus primarily transmitted through the bite of Aedes or Haemagogus mosquitoes. Endemic to tropical and subtropical regions of Africa and Latin America, YFV causes significant public health concerns. It has been estimated that up to 1.7 million YFV infections occur in Africa each year, resulting in 29,000 to 60,000 deaths. In fact, in 1793, there was a YF epidemic in Philadelphia killing around 1/6th of the population. The virus is responsible for yellow fever, an acute hemorrhagic disease characterized by fever, jaundice, and in severe cases, organ failure and death. Thus far, there has been no specific antiviral treatment for yellow fever; however, researchers have identified Benzodiazepine Acetic Acid (BDAA), a compound that inhibits YFV by targeting the viral NS4B protein, as a possible therapeutic option. While current treatments focus solely on managing symptoms, antiviral treatments directly target the virus during the course of infection, reducing viral replication and severity of symptoms. This reveals that an antiviral option could be more effective than the traditional treatment. In order to create analogues of different potencies and efficacies of the compound, this project aimed to find the 3D structure of BDAA. To do this, a single crystal growth was created using a method called vapor diffusion. The single crystal growth produced was mounted in an X-Ray diffraction machine. Using the angles and intensity of the light that diffracted through the crystal, a 3D structure was computed, which further confirmed the arrangement of atoms in 3D space. Future research would include determining possible binding sites and performing comparative studies utilizing the compound.
Athena Man is a CB East junior who will return to the Biotech Center for her senior year. She likes playing the drums.
Jaden Young
Jaden Young received nominations and appointments to the United States Military Academy at West Point, the United States Naval Academy, AND the United States Air Force Academy. Our congressional district is the most competitive nationwide for admission to the service academies, and his appointments occurred very rapidly. Jaden was selected as one of fewer than ten applicants from a pool of thousands to bypass the application process for immediate enrollment in the Martinson Honors Program at the Air Force Academy.
Jaden has decided that he will attend the United States Military Academy at West Point. In opting to serve our country, Jaden has decided against attending numerous top-tier universities, earning over $2 million dollars in scholarship offers. Some of those universities include:
Boston University (Honors College and Full-Ride Scholarship), Boston College (Full-Ride Scholarship), Clemson University (Honors College and Full-Ride Scholarship), LSU (Honors College and Full-Ride Scholarship), University of Florida (Distinguished Academic Scholarship), University of Southern Carolina (Honors College and Superlative Academic Scholarship), Penn State (Honors College and Schreyer Scholarship)
Annalisse DeSandre
Attending Hofstra University and Zucker School of Medicine in the 4 + 4 BS/MD Program minor, one of only 15 accepted into the program. Annalisse will major in bioengineering and minor in economics.
Sophia Fehrenbach
Pursuing a degree in Molecular Biology on the pre-med track. Sophia is enrolled in the Frederick C. Davis Honors College.
Madison Oh
Attending the University of North Carolina- Chapel Hill. Will likely pursue a degree in health policy & management in the Gillings School of Public Health on the pre-med track.
Diya Mahesh
Will attend Johns Hopkins University where she will study chemical and biomolecular engineering
Semen Sakhabutdinov
Will study biochemistry and neuroscience at Brown University. Semen is a QuestBridge Match Scholarship (full-ride) recipient.
Jillian Walworth
Attending University of Pennsylvania. Pursuing a degree in materials science and engineering.
Eepsitha Popuri
Attending the University of California- San Diego and pursuing a degree in public health with concentration in medicine sciences.
Soumil Sharma
Attending the University of Pennsylvania. Soumil will likely study either biophysics or neuroscience on the pre-med track
