Research Teams

Our research at Penn State University uses innovative approaches to study human development and disease. In particular, we use a combination of structural and functional tools to investigate how cells communicate with each other. Protein receptors found on the surfaces of cells transmit signals from the external environment into the cell’s nucleus to turn on genes at the appropriate time. Poorly transmitted signals between cells or within cells result in a myriad of diseases including cancer. We would like to better understand how these signaling mechanisms drive tumor initiation. Cryo-Electron Microscopy (EM) is an ideal technique to visualize cells and macromolecular assemblies at high-resolution. We use cryo-EM to investigate how cancer cells differ from normal cells. Problems with the structural integrity of these receptors cause a small population of cells to migrate away from a primary tumor site and reattach elsewhere in the body, a process called metastasis. Our newly developed Affinity Capture platform allows us to isolate the cells that cause metastasis and study their molecular landscapes at unprecedented resolution. https://www.debkellylab.org/

A structural study offers a powerful tool of direct visualization that can guide and complement other research approaches. Cryo electron microscopy (CryoEM) allows three-dimensional imaging at the subcellular level, filling a gap between the atomic resolution provided by NMR and Xray, and visualization by light microscopy of larger entities such as bacteria, whole cells and organelles.

We use a structural approach to learn more about viral infectivity, tropism, evolution and pathogenicity. Of particular interest are conformational changes of the virus capsid structure that occur as a response to key events that direct a successful infection, such as receptor binding prior to host entry. We are also developing approaches to visualize critical events that cause a break from the regular symmetry of the virus, including packaging of the genome, receptor usage, antibody interactions, and uncoating of the viral genome during the final stages of infection.

http://php.scripts.psu.edu/dept/hafenstein/index.php

Hedglin Lab

The genetic information (i.e., genome) of a human cell is encoded in strands of DNA that assemble into an antiparallel DNA double helix. Each time a cell divides, the genome must be faithfully replicated and transferred to a daughter cell for genetic inheritance. The former occurs during S-phase of the cell cycle and relies on high-fidelity, i.e. “replicative,” DNA polymerases that read template DNA strands and synthesize their complementary DNA. Additional “core” proteins and enzymes are also involved and the basic mechanism of human DNA replication has been deciphered. However, it is currently unknown how DNA replication is achieved on genomic DNA within a human cell. We aspire to decipher how efficient and faithful replication of the human genome is achieved within the highly-complex, dynamic, and reactive cellular environment. We employ a collaborative approach, combining biophysical, biochemical, and molecular and cellular biology techniques to; 1) identify cellular factors involved in various aspects of human DNA replication and; 2) re-constitute human DNA replication in various biological scenarios and at various levels of complexity.

https://sites.psu.edu/hedglinlab/

Pritchard Lab

Penn State’s Pritchard Lab merges the study of biomedical engineering and biological evolution. Led by Dr. Justin Pritchard, the lab’s research team uses engineering design to build cell systems, then they test their ability to control and understand the way populations of cells evolve. The team of scientists combine cell engineered models and quantitative experiments to better understand the design principles of successful small molecule therapy.

https://sites.psu.edu/pritchardlab/the-lab/

Varano Lab

Cancer diagnoses in the U.S. will affect nearly 2 million individuals this year. It will claim the lives of over 600 thousand Americans patients according to the American Cancer Society. Metastatic cancer, the spread of cancerous cells throughout the body, is the primary cause of cancer-related death. Research shows early detection leads to greater patient survival. It is imperative that we understand the signature of cancer and its ability to spread throughout the body. My research interest is in developing technology to detect metastatic cancer before it proliferates to healthy tissue. Cancer cells use exosomes to engineer the tissue microenvironment prior to their migration. Consequently, understanding exosomes can help predict disease staging. Their signature is key to identifying unique features of metastasis.

https://www.bme.psu.edu/department/directory-detail-g.aspx?q=acv5167