Postdoctoral Training

The postdoctoral training program is designed to provide training in the conduct of scholarly investigation in one of the four scientific areas of expertise of the Cancer Biology Training Grant preceptors. The training is designed for biomedical scientists who have a Ph.D. in basic science (biochemistry, cell biology, genetics, microbiology, immunology, etc.) and for physicians who have basic research experience and interest in the areas studied by the preceptors. Support for postdoctoral trainees is typically for two years. However, all postdoctoral trainees are encouraged to apply for independent postdoctoral funding while they are being supported on the training grant.

Interested postdoctoral fellows currently training in a preceptor's laboratory may apply for support on the Cancer Biology Training Grant when a position becomes available. All positions are selected on a competitive basis by the Cancer Biology Training Grant Steering Committee. Contact the Cancer Biology Training Grant Director for information on how to apply.

If you are interested in postdoctoral training with one of our preceptors, you may contact them directly or direct an inquiry to Carol Lange, PhD at

Current Trainees:

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Ya Chu Chang, PhD 

Nguyen Lab

Mechanisms of PARP inhibitor sensitivity in MDS. Myelodysplastic syndrome (MDS), a heterogeneous group of clonal hematopoietic stem cell disorders, is a common adult myeloid malignancy that can transform into chemo-resistant secondary acute myeloid leukemia (sAML). Somatic heterozygous mutations in spliceosome (SF) genes (SF3B1, U2AF1, SRSF2, and ZRSR2) occur in over 50% of MDS patients and are mutually exclusive. In particular, SRSF2 and U2AF1 gene mutations are associated with worse overall survival and an increased risk of transformation to sAML. SF mutations also occur early in disease development, highlighting a unique genetic vulnerability for therapeutic development. Our lab revealed that SF-mutant leukemias were sensitive to a poly(ADP-ribose) polymerase (PARP) 1 inhibitors (PARPi). The hypersensitivity to PARPi was partly due to increased PARP1 activity in SF-mutants, required for alleviating accumulated R loops, a group of transcription intermediates containing RNA:DNA hybrids and a displaced single-stranded DNA. We hypothesize that SF mutations disrupt multiple pathways beyond R loops accumulation that require PARP1 activity for survival. We aim to elucidate mechanisms that confer PARPi sensitivity by examining how SF-mutants trigger PARP1 response and determining pharmacologic and genetic vulnerabilities that further sensitize SF-mutant leukemias to PARPi. The results from the proposed studies will significantly advance our understanding of PARP1 signaling and repurpose the use of FDA-approved PARP inhibitors as mono- or combined- agent in targeted therapy for MDS patients harboring SF mutations.

Jason Jones, PhD

Jason Jones, PhD 

Levinson Lab

In search of the structural mechanisms regulating paradoxical activation of BRAFV600E driven cancers. Over 50% of melanoma tumors harbor a mutation in the protein kinase BRAF and 90% of these tumors have the infamous V600E mutation. The current FDA-approved drugs potently inhibit BRAFV600E monomers, but do not inhibit BRAFV600E dimers, and instead elevate their activity through a phenomenon termed, inhibitor-induced paradoxical activation. The inability of BRAF inhibitors to effectively inhibit BRAFV600E dimers highlights the need to develop new therapeutic strategies that effectively inhibit BRAFV600E dimers and avoid the negative outcomes of paradoxical activation. To date, the structural mechanisms regulating BRAF paradoxical activation are not completely understood. We aim to solve this mystery by obtaining  molecular structures of isolated BRAF and BRAF bound to paradoxically-activating inhibitors by utilizing single-particle cryogenic electron microscopy. To better combat BRAF-driven cancers like melanoma, we must gain a precise understanding of the structural mechanisms responsible for paradoxical activation.

William Kanagy, PhD

Freedman Lab
Differential signaling of LynA and LynB dependent on immune receptor signaling motifs. The Src-family kinase Lyn phosphorylates immune receptors in myeloid and B cells. In the context of cancer, Lyn dysregulation suppresses myeloid cell activation and results in the progression of leukemia, glioma, and breast cancer. Lyn phosphorylates both immune activating ITAM (e.g., CD16) and suppressive ITIM (e.g., CD32b) receptors. Melanoma studies show that Lyn-mediated CD32b ITIM signaling promotes immunosuppression in those tumors. Conversely, increased macrophage CD16 ITAM activation via Lyn improves survival of colorectal cancer patients by promoting antibody-dependent cellular phagocytosis. These studies highlight the finely tuned relationship between Lyn, ITAMs, and ITIMs, promoting either immune cell evasion or activation. The underlying mechanisms as to how Lyn drives either immune activation or immunosuppression in cancer remains a mystery. Dr. Freedman’s lab has begun to clarify the dual signaling roles of Lyn by identifying divergent roles of the two isoforms, LynA and LynB. Recently our lab defined a unique facet of LynA regulation, where activation of LynA results in phosphorylation of LynA tyrosine residue (Y32) and triggers LynA degradation via polyubiquitination by the E3 ligase c-Cbl. LynB lacks Y32 and is thus more resistant to degradation, suggesting LynA provides an acute signaling “burst” after activation, but LynB may be required to promote prolonged signaling responses. As a lab we have recently generated single-isoform LynA- and LynB-specific knockout (KO) mice which I will use to precisely study LynA and LynB signaling mechanisms at the CD16 ITAM or CD32b ITIM interface. Elucidating the mechanisms by which LynA and LynB differentially promote activation or immunosuppression will allow for more precise reversal of cancer evasion and induction of cancer-cell killing. 

Megan Ludwig, PhD
Drake Lab

Extracellular vesicles (EVs), such as exosomes, are particles that are exported from cells for intercellular communication and contain cargo that can reveal important information about activated signaling networks. We think that proteins, especially phosphoproteins, expressed in EVs may have functional relevance, impacting therapeutic resistance through autocrine or paracrine transfer of critical signaling cargo. Our objective is to understand the composition and function of proteins expressed in EVs and how they contribute to mechanisms of resistance in prostate cancer.

Alex Tsai, PhD 

Stromnes Lab

Instructing engineered T cell fate by defining optimal T cell receptor affinity and abrogating tumor growth factor-beta receptor 2. T cell receptor (TCR)-engineered cell therapies have shown efficacy targeting advanced solid tumors. More investigations are needed to further refine and optimize these therapies. Both the affinity of engineered TCR and tumor antigen are key determinants of adoptive cell therapeutic efficacy. We have generated a novel mouse model in which high- and low-affinity TCRs specific to the well-established tumor antigen, mesothelinin, were inserted into the T cell receptor alpha constant (Trac) locus) of mouse zygotes via CRISPR/Cas9. The model allows for direct comparison between TCRs with varying antigen-MHC affinity that are expressed in an endogenous manner. Using this model, we will determine the role of TCR affinity and tumor antigen levels on the fate, functionality, and longevity of TCR-engineered T cells by evaluating efficacy of adoptive T cell therapy in several syngeneic faithful models of cancer, including pancreatic ductal adenocarcinoma, triple-negative breast cancer, and mesothelioma. Numerous immunosuppressive mechanisms are present in the tumor microenvironment that lead to T cell dysfunction, even in those with optimal TCR affinity. Tumor growth factor-beta (TGFβ) is overexpressed in many cancers. In T cells, signaling is mediated in part through TGFβ receptor 2 (Tgfbr2) and leads to T cell tolerance. Thus, we will simultaneously determine if abrogating Tgfbr2 safely improves adoptive T cell therapeutic efficacy. Murine studies will use T cell-specific Tgfbr2 knockout mice crossed to the aforementioned mesothelin TCR mice and the syngeneic faithful models previously discussed. Human TGFBR2-null cells will be generated via base editing with efficacy evaluated in immunodeficient mice bearing human pancreatic tumors.

Previous Trainees:

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Ethan Aguilar, PhD

Blazar Lab 

Constance Anderson, PhD

Harki and Drake Labs

Prostate cancer (PCa) is the most frequently diagnosed cancer among American men. Although PCa patients have a 97.5% five-year survival rate, those with metastatic or recurrent PCa have much lower five-year survival outcomes of 30.6%. While second-generation androgen deprivation therapies (ADT) are used as life-extending treatment for metastatic castration-resistant prostate cancer (mCRPC) patients, this leads to the development of ADT-resistant, aggressive variant prostate cancer (AVPC), including molecular subtype neuroendocrine prostate cancer (NEPC). There is an urgent need to develop new treatments for NEPC due to the current lack of effective options. Previous data from our labs suggest that NEPC tumors require activated RET kinase to survive, indicating that RET receptor tyrosine kinase is a novel therapeutic liability in NEPC. Despite this, RET kinase inhibitors have shown disappointing results as mCRPC therapeutics in clinical trials. In recent years, a new modality of drug discovery has emerged using heterobifunctional molecules, or PROTACs (Proteolysis Targeting Chimeras) to achieve targeted protein degradation. PROTACs link recognition moieties for a protein of interest (POI) with an E3 ubiquitin ligase to induce polyubiquitination of the POI, leading to degradation through the native cellular proteasome system. I am developing RET-targeting degraders using RET-binding ligands conjugated to thalidomide, a ligand for the E3 ubiquitin ligase cereblon. I am currently pursuing the synthesis of two scaffolds with various covalent linkers to optimize RET-binding properties and degradation efficiency. Once developed, I will characterize the degraders using kinase-specificity and cellular assays. I hypothesize that targeting RET for degradation will induce NEPC cell death that is more durable than existing RET kinase inhibitors due to degradation of RET rather than transient inhibition of its enzymatic activity.

Julia Austin, PhD
Lange Lab

Breast cancer is a significant health burden. The type of breast cancer is determined by the presence or absence of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor 2 (HER2) gene amplification. Hormone-blocking (anti-estrogens, aromatase inhibitors) therapies in combination with CDK4/6 inhibitors are highly effective for most ER+ cases. In triple negative breast cancer (TNBC), which lacks these receptors, treatment usually involves chemotherapy, which targets proliferating cells, leaving viable quiescent cancer cells. Recent research has uncovered that the glucocorticoid receptor (GR) is involved in breast cancer. In TNBC, GR is associated with chemoresistance and disease recurrence. GR upregulates genes involved in cell migration and invasion. The Lange lab discovered that GR is more cytoplasmic and phosphorylated on Ser134 in TNBC relative to ER+ cases and that pSer134-GR is required for TNBC cell migration. In luminal breast cancer, however, GR is associated with increased survival. Understanding the opposing actions of GR in luminal breast cancer relative to TNBC may provide important clues as to why GR expression is deadly in TNBC. By comparing GR functions in experimental models of both ER+ and TNBC, we aim to discover why GR is protective in ER+ breast cancer, yet oncogenic in TNBC. To discover this, the ligand-activated GR transcriptome in ER+ breast cancer compared to TNBC will be determined. The signaling events that are linked to GR-induced stemness properties in TNBC will also be determined to characterize the oncogenic role of GR in TNBC. This research will identify novel signaling inputs to GR-induced breast cancer stemness properties that could lead to new cancer targets aimed at non-proliferating cells in TNBC.

David Burban, PhD

Bio coming soon.

Lynsey Fettig, PhD

Yee Lab

Joseph Greene, PhD

Bio coming soon.

Harris Krause, PhD

Provenzano Lab

Metastatic recurrence, which often results in patient death, occurs when dormant disseminated tumor cells exit dormancy and begin proliferating. The extracellular cues and molecular mechanisms that underpin this phenomenon are poorly understood. This is partly due to a lack of high throughput in vitro models of tumor dormancy. In vitro, microtissues, consisting of breast cancer cells cultured in droplets of ECM will be created to mimic the dormant microenvironment. The microtissues will be created using high throughput microfluidics, with an array ECM components and extracellular factors tuned to induce dormancy in the cells. Fluorescent reporters will be used to identify cells that are expressing markers for either proliferation or dormancy. Microtissues can then be sorted into dormant of proliferative populations. This will allow for combinations of ECM that act synergistically to induce dormancy to be identified. Dormant and proliferative subpopulations will undergo RNA-seq after sorting to identify novel molecular signatures for both entrance into and maintenance of dormancy. Next, we will conduct a genome wide knock out screen using CRISPR/CAS9 to identify genes and pathways that are essential to dormancy entrance and maintenance. Novel targets will be validated using siRNA and small molecule inhibitors. Further validation will be done in vivo with mouse models of tumor dormancy.

Chelsea Lassiter, PhD

Schwertfeger lab
Phone: 612-626-5059

Immunotherapy has shown promise in some solid tumors including breast cancers with high levels of tumor infiltrating lymphocytes (TILs). In other cancers, enhancing T cell infiltration into tumors that lack significant levels of TILs enhances responsiveness to immune based therapies (TILs). TIL infiltration is found in approximately 20% of triple negative breast cancers (TNBCs) and correlates with favorable patient outcome. Therefore, developing approaches to enhance T cell infiltration into primary and metastatic lesions could enhance the percentage of breast cancer patients that respond to immunotherapy.

The signal transducer and activator of transcription (STAT) protein family regulates gene expression changes related to proliferation, apoptosis, and immune response. Constitutively active STAT3 is found in 70% of human solid tumors and regulates immune response to tumor cells.  STAT3 is a potent oncogene and a promising target for immunotherapy. Our lab has shown that a loss of STAT3 leads to an increase in a potent tumor suppressor, STAT1, in multiple cell types. There is also an increase in immunomodulatory genes. In addition, we see a compensatory increase in an immune checkpoint protein, PD-L1, expressed by tumor cells and macrophages

We predict that STAT3 inhibition will enhance T cell infiltration into tumors through increased expression of T cell chemokines, although this will not be sufficient to elicit an anti-tumor response due to increased PD-L1 expression. Therefore, we hypothesize that selectively inhibiting STAT3 and PD-L1 will increase recruitment and enhance activation of T cells at the tumor site, and lead to an effective anti-tumor immune response. 

Kelly Makielski, PhD

Modiano Lab

Osteosarcoma (OSA) is an uncommon but devastating bone cancer, typically diagnosed in children and adolescents. Despite aggressive treatment, many affected children develop metastatic disease for which there is no effective therapy. Despite advances in cancer therapy, the prognosis with OSA has remained stagnant for over thirty years, highlighting the need for novel treatment strategies. OSA is an immune responsive tumor, making immunotherapy a promising new treatment. One approach to activate the immune system is with oncolytic viruses, such as vesicular stomatitis virus (VSV). Oncolytic viruses selectively replicate in and destroy tumor cells, exposing viral antigens and tumor-associated antigens, triggering an anti-tumor immune response to potentially delay or prevent metastases.

Pediatric OSA research is hindered by its rarity, with fewer than 1,000 new cases diagnosed annually. In contrast, OSA occurs commonly in dogs, and its comparable clinical presentation makes the dog a useful model for translational OSA research. We have previously shown the existence of two molecular OSA phenotypes with distinct biological behavior and prognosis, characterized by both intrinsic tumor properties and host factors. This provides the opportunity to test experimental therapies on two disease phenotypes expected to have different prognoses with standard of care alone.

We are investigating the potential of oncolytic virotherapy with VSV to initiate anti-tumor immunity in canine OSA, with the intent to inform future clinical trials for human patients. Dogs with naturally-occurring OSA will be administered oncolytic VSV in addition to standard of care. We will characterize the anti-tumor immune response induced by VSV, and correlate it with the presence of resident or infiltrating immune cells in the tumor, as well as with clinical endpoints, including time to metastasis and survival time.

We hypothesize that VSV treatment will increase infiltration of immune cells into tumors, generating clonal populations with anti-tumor activity. We anticipate that this immune activation will be associated with improved survival compared to that expected with standard of care alone.Our results will provide valuable information regarding the mechanisms of immune activation by VSV and its potential translation to humans with OSA and other tumors. Determining prognostic factors will help guide treatment decisions, targeting VSV therapy primarily toward patients expected to respond favorably.

Milagros Silva Morales, PhD

Mueller lab

Peripheral Immune Self-Tolerance Mechanisms: Anergy, Treg cells and Cancer
Peripheral tolerance is a necessary mechanism to control auto-reactive lymphocytes outside of the thymus. Anergy is a peripheral tolerance mechanism wherein self-reactive lymphocytes become unresponsive after antigen encounter but remain alive. Anergic CD4+ T cells lose their ability to produce growth factors such as IL-2 in response to antigen and develop poor proliferation. Recently, our laboratory reported on an anergic subset of naturally occurring Foxp3CD44hiCD73hiFR4hi polyclonal CD4+ T cells in healthy hosts. Responder CD4+ T cells with this phenotype could also be induced in response to recognition of fetal anti­gens during pregnancy. Interestingly, more than 80% of anergic T cells also specifically expressed the semaphorin receptor Nrp1 by day 18 of pregnancy. Foxp3+ Treg cells are also essential for peripheral immune tolerance and for anergy induction. Remarkably, polyclonal anergic CD4+ T cells can be induced to differentiate into Treg cells when they are adoptively transferred to a lymphopenic host. In particular, Nrp1+ anergic conventional CD4+ T cells displaying a partially de-methylated tTreg-me signature gave rise to functional Foxp3+Nrp1+ pTreg cells with a fully de-methylated Treg-me signature in vivo.

T cell anergy is proposed to be a cellular mechanism of immune evasion contributing to the failure of T cells to eradicate tumors. Tumor antigens can be taken up and presented by APCs in the absence of co-stimulatory signals promoting anergy in antigen-specific CD4+ T cell populations. In addition to anergy, regulatory T cells also have a principal role in promoting immune evasion by cancer cells. Foxp3+ Tregs are specifically recruited to the tumor sites and suppress tumor-specific T cell responses. Their abundant presence is one of the major obstacles to effective antitumor immunotherapy and it is often associated with poor clinical prognosis. In spite of these important discoveries the role of Treg in cancer is controversial. Finally, Nrp1 up-regulation appears to be associated with the tumor invasive behavior and metastatic potential. Increased levels of Nrp1 correlate with tumor aggressiveness, advanced disease stage, and poor prognosis.

Our hypothesis for why Treg cells arise in tumors is that Nrp1+ anergic CD4+ T cells are ideal progenitors for Foxp3+ Treg cells. The objective of my project is to specifically study the role of Nrp1 on the induction of CD4 T cell anergy and the trans-differentiation of anergic conventional T cells into the Foxp3+ Treg cell lineage.

Erica Pratt, PhD

Parker Lab

Bio coming soon

Zoi Sychev, PhD

Drake Lab

Evaluating the protein expression of AR-Vs landscape in Prostate Cancer. Prostate cancer (PCa) is the most diagnosed cancer in men in the United States. Typical upfront treatment involves targeting the androgen receptor (AR) using Androgen Deprivation Therapy (ADT), While effective initially, tumors typically progress to metastatic castration resistance prostate cancer (mCRPC) at which point second generation hormonal therapies, abiraterone acetate (Abi) and enzalutamide (Enza) are administered. Emergence and increased expression of AR isoforms (AR-V) have been associated with Abi and Enza drug resistance. Approximately 18 DNA and mRNA molecules of AR-Vs have been identified in bulk cancer cells but the quantitative assessment of AR-V proteins have not been directly measured with the exception of AR-V7. We hypothesize that, in addition to AR-V7, expression of other AR-V proteins contributes to ADT resistance. To study this, we developed a targeted mass spectrometry-based (T-MS) proteomics platform to identify and quantify most of the AR-V proteins from different clinical specimens. Our overarching goal is to apply the AR-Vs Targeted MS (ARvT-MS) platform to assess clinical samples, including exosomes and CTCs, and to develop a more comprehensive AR-V protein based predictive biomarker platform to better stratify patients with mCRPC. Our objective in this proposal, is to continue assessing the proteome landscape of AR-Vs in cell lines, tissues and then correlate our findings with clinical CTCs from mCRPC patients.

Kiel Tietz, PhD

Dehm Lab

Throughout my career I have always been interested in mechanisms of RNA processing that become dysregulated in disease and cancer. mRNA polyadenylation plays a critical role in stability, translation, and defining the 3’ end of a transcript and our work has identified alternative polyadenylation of the androgen receptor (AR) as a mechanism that is manipulated in metastatic prostate cancer for continued growth. My project focuses on defining the mechanisms that drive alternative polyadenylation of AR in metastatic prostate cancer to determine specific sequence elements and trans-acting factors that can be targeted for more effective treatment of metastatic prostate cancer in patients.