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Your paper and your thesis

The two pieces of your own work they may ask about. Read this once Thursday. Each part ends with a short German version you can say out loud.

Read this before anything else. In the published Cells paper you are the 4th of 11 authors. The first author is Dr. Luca Hegedüs. Your CV (“Erstautor”) and your UKSH cover letter (“Erstautorschaft”) say you are the first author. The panel can check this in seconds. In the interview, say Mitautor (co-author). If someone says “Sie sind Erstautor”, correct it calmly: “Kleine Korrektur: Ich bin Mitautor, Erstautorin ist Dr. Luca Hegedüs.” A calm correction is much better than being caught.

Cells 2025 · 14(20):1599

The Cells paper (CUDC-907)

Hegedüs L, Qaisieh S, Stülpnagel C, Ganjeh Khor Dezfouli Y, Tambo W, Doerr F, Baldes N, Theegarten D, Schuler M, Bölükbas S, Hegedüs B. Dual HDAC and PI3K Inhibitor CUDC-907 Inhibits Growth of Pleural Mesothelioma: The Impact of Cisplatin Sensitivity and Myc Expression. Cells 2025, 14, 1599. Published 15 October 2025. doi:10.3390/cells14201599

The abstract in plain words

Problem: pleural mesothelioma is rare, appears decades after asbestos exposure, and has a poor prognosis. New treatments chosen by biomarkers are needed.
Drug: CUDC-907 (fimepinostat) blocks two targets at once: histone deacetylases (HDAC class I and II) and PI3K. It had never been tested in mesothelioma.
What was done: 22 mesothelioma cell lines (18 established in the Essen lab) were tested with cisplatin and CUDC-907 in viability assays. BAP1, PTEN and c-Myc expression and MYC copy number were measured. Combinations with cisplatin were tested by viability, cell cycle and 3D spheroid assays.
Results: most lines were sensitive to CUDC-907. Lines with more c-Myc (from MYC copy gain or amplification) responded more strongly. Every cisplatin-insensitive line was still sensitive to CUDC-907. CUDC-907 plus cisplatin was synergistic and caused G2/M arrest or cell death. In a matched pair (P31WT sensitive, P31cis cisplatin-resistant), the resistant cells were more sensitive to CUDC-907, in 2D and in 3D.
Conclusion: most mesothelioma models respond to CUDC-907, so it may be a useful drug for this cancer.

Terms to have ready

Synergy

Two drugs together work better than their single effects added up.

Isogenic pair

The same cell line in two versions (here: normal and cisplatin-resistant), so only resistance differs.

MYC copy number

Extra copies of the MYC gene raise c-Myc protein. Here that predicted a better response.

A bridge to hematology: the paper notes that the FDA gave CUDC-907 fast-track status in 2018 for diffuse large B-cell lymphoma (DLBCL) after two or more prior therapies. MYC is also a key driver in aggressive lymphomas. That links your paper to their field.

Before Friday: fill this in yourself

Write down in one sentence what you did for this paper (for example, which assays or cell lines). I can't see that in the paper, so it's not filled in here. Only say what you actually did.

Sprechvorlage

Ich bin Mitautor einer Studie in Cells aus der Arbeitsgruppe in Essen. Wir haben den dualen HDAC- und PI3K-Hemmer CUDC-907 an 22 Mesotheliom-Zelllinien getestet. Die meisten Linien waren empfindlich, besonders solche mit hoher c-Myc-Expression, und auch cisplatin-resistente Zellen sprachen an. Mein Beitrag war [ … ].

B.Sc. Bioengineering · Hochschule Rhein-Waal · July 2025

Your bachelor thesis

Title: The effect of TFEB inhibitor treatment on TROP2 expression in Pleural Mesothelioma cells (title in your final draft of 26 July 2025; your CV uses a different title, so check which one is on your certificate)
Supervisors: Prof. Dr. Mònica Palmada Fenés (HSRW), Dr. Balazs Hegedüs (Ruhrlandklinik Essen)
Host: University Medicine Essen – Ruhrlandklinik

The story in five steps

Why: TROP2 is a surface protein on many cancers, including mesothelioma. The antibody-drug conjugate sacituzumab govitecan binds TROP2, so it only works if TROP2 sits on the cell surface.
Idea: autophagy, controlled by the transcription factor TFEB, may break down TROP2. Blocking autophagy might keep more TROP2 on the surface.
Design: 6 cell lines (PF155, PF626, PF760, SPC212, PF774, PF998). Nintedanib (1 µM), the autophagy inhibitors VPS34-IN-1 (2 µM) and Eltrombopag (15 µM), alone and combined.
Methods: SRB viability assays with IC50, Western blot for TROP2, TFEB and β-catenin (β-actin as loading control), and flow cytometry for surface TROP2 with unstained and isotype controls.
Findings:
- VPS34-IN-1 was more toxic than Eltrombopag. PF626 was the most sensitive line, PF998 the least.
- Baseline surface TROP2 differed a lot: 44% of SPC212 cells were TROP2-positive, but only 1% of PF998.
- Nintedanib alone raised TFEB, a sign of lysosomal stress. Combined with autophagy inhibitors, TFEB went down, and on Western blots TROP2 was highest with Nintedanib + Eltrombopag.
- The TFEB response depended strongly on the cell line: clear in PF155 and PF626, absent in PF774 and PF998.

The limitations (your best interview material)

Autofluorescence: Nintedanib forms crystals in lysosomes and fluoresces. So you could not measure Nintedanib-treated samples by flow cytometry and evaluated only the other conditions.
Flow cytometry worked well in 3 of 6 lines only.
The link between TFEB and TROP2 is a correlation. There was no TFEB knockdown to prove cause.
Morphology images were judged by eye, not quantified.

Why this matters for UKSH: excluding the Nintedanib flow data was a plausibility decision. You saw that the signal came from the drug, not from the antibody, and you did not report it as a result. That is the same thinking they need when checking patient measurements. Use it for the questions on implausible values and on a failed experiment.

Sprechvorlage, 30 Sekunden

In meiner Bachelorarbeit habe ich untersucht, ob die Hemmung der Autophagie die Menge von TROP2 auf Mesotheliomzellen verändert. TROP2 ist das Zielprotein eines Antikörper-Wirkstoff-Konjugats, das nur wirkt, wenn TROP2 auf der Zelloberfläche sitzt. Ich habe sechs Zelllinien mit Nintedanib und zwei Autophagie-Hemmern behandelt und mit SRB-Assays, Western Blot und Durchflusszytometrie ausgewertet. Die Oberflächenexpression war sehr unterschiedlich, von 44 Prozent bis 1 Prozent positiver Zellen, und die Kombinationen haben TFEB gesenkt. Eine wichtige Erfahrung war die Eigenfluoreszenz von Nintedanib: Diese Proben konnte ich durchflusszytometrisch nicht verlässlich messen und habe sie deshalb bewusst nicht ausgewertet.

Tap to open

Questions about your thesis

Was war die größte Schwierigkeit?What was the hardest part?

Die Eigenfluoreszenz von Nintedanib. Das Medikament lagert sich in den Lysosomen ab und fluoresziert selbst. In der Durchflusszytometrie hätte das wie eine TROP2-Färbung ausgesehen. Ich habe das anhand der Kontrollen und der Literatur erkannt und diese Proben deshalb nicht ausgewertet, statt falsche Werte zu berichten.

This also works as your “failed experiment” story.

Warum Isotypkontrollen?Why isotype controls?

Die Isotypkontrolle zeigt, wie viel Signal durch unspezifische Bindung des Antikörpers entsteht. Nur was deutlich darüber liegt, werte ich als echte Färbung. Zusammen mit der ungefärbten Probe sehe ich auch die Eigenfluoreszenz der Zellen.

Was würden Sie heute anders machen?What would you do differently?

Ich würde den Zusammenhang zwischen TFEB und TROP2 mit einem TFEB-Knockdown direkt prüfen und für die Durchflusszytometrie einen Kinasehemmer ohne Eigenfluoreszenz wählen. Außerdem würde ich die Morphologie quantitativ auswerten, statt nur Bilder zu vergleichen.

Wie sicher sind Ihre Ergebnisse?How solid are your results?

Stay modest: these are first indications in cell lines, partly from single experiments, and the TFEB–TROP2 link is a correlation. Say “Hinweise”, not “Beweis”. Labs that do diagnostics value people who don't overstate results.

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